Podcasts about Pyxis

“Always test your tools before field use. Side-by-side comparisons ensure repeatability and accuracy.” In this episode of Scaling UP! H2O, host Trace Blackmore delivers an in-depth update on the SteriPen, a widely used tool for water treatment professionals. After overwhelming demand from listeners, we revisit the SteriPen, its capabilities, and its impact on testing organic phosphates and azoles. If you're looking for efficiency, precision, and portability in water testing, this episode is packed with actionable insights.  The Evolution of the SteriPen Learn how the SteriPen became a game-changer in the industrial water treatment industry. Originally designed for hikers, it's now widely adopted for phosphate digestion and azole testing.  SteriPen Classic 3 vs. SteriPen Ultra: Which One Is Right for You? Trace compares the Classic 3 and Ultra models, discussing their battery life, efficiency, usability, and cost-effectiveness. Get clarity on which device suits your testing needs best.   Testing Efficiency: Reducing Time While Maintaining Accuracy Find out how the SteriPen reduces testing time by half while maintaining accuracy, making it a must-have tool for water professionals.  Best Practices for SteriPen Use From choosing the right vials and batteries to ensuring consistent testing results, this segment walks you through practical applications and expert recommendations.  The Future of Water Testing How innovations like the SteriPen and other portable UV tools are reshaping the way industrial water treatment professionals conduct daily testing.  With water testing advancements, efficiency is key. Whether you're new to SteriPen or looking to upgrade, this episode provides valuable insights to optimize your water testing process.  Water professionals deserve better tools. Upgrade your phosphate and azole testing with the right SteriPen for maximum efficiency and accuracy.  Stay engaged, keep learning, and continue scaling up your knowledge!    Timestamps 02:28 – Trace Blackmore shares a recap of Episode 414 06:47 – Upcoming Events for Water Treatment Professionals   16:15 – Water You Know with James McDonald  20:45 – Deep dive into SteriPen device: it's history and application 33:29 – Comparison between SteriPen Classic 3 and SteriPen Ultra  36:00 – Testing Procedures for organic and phosphate and azole tests  38:02 – Charging and battery life for both SteriPen models    Connect with Scaling UP! H2O Submit a show idea: Submit a Show Idea LinkedIn: in/traceblackmore/  YouTube: @ScalingUpH2O  Click HERE to download Episode's Discussion Guide      Scaling UP! H2O Resources Mentioned  Ep 046 The One About Phosphate Testing Ep 414 Pinks and Blues: Trace's Phosphate Redux Ep 415 Green Building Updates: What You Need to Know AA Battery Cases Augmenting your testing procedures for Phosphonate and Azole testing AWT (Association of Water Technologies)   Energizer Ultimate Lithium AA Batteries Eowpower 30pcs 50ml Plastic Vial Storage Container  Hach UV Lamp Kit, 115V  Hach Benzotriazole/Tolyltriazole  Hach Orthophospate PhosVer 3  Hach Phosphonate Lithium re-chargeable batteries  Re-chargeable Lithium Batteries with charger  Scaling UP! H2O Academy video courses  Steri Pen Classic 3  SteriPen Ultra  SteriPen Ultra – Katadyn Fact Sheet Submit a Show Idea  The unboxing of everything you need to use the SteriPen in your Phosphonate and Azole testing  Taylor Technologies Test Procedures:  Phosphonate  Taylor Technologies Test Procedures: Azole  World Vision Global 6k for Water    Water You Know with James McDonald Question: Does silica solubility typically decrease or increase with rising temperature?    2025 Events for Water Professionals  Check out our Scaling UP! H2O Events Calendar where we've listed every event Water Treaters should be aware of by clicking HERE. 

So many new gear updates have dropped recently due to NAB Show 2025—it's almost overwhelming to keep track! But don't worry—sit back, relax, and check out this week's episode of FocusCheck for all the highlights and key updates. From cameras and lenses to lighting and software, we've got everything covered in one easy-to-digest episode. Enjoy! Sponsor: This episode is sponsored by FUJIFILM. Check it out at (34:36) Chapters & Articles Mentioned in This Episode: (00:00) -  Intro (02:07) - Blackmagic Design NAB 2025 Update – Join the Live Stream https://www.cined.com/blackmagic-design-nab-2025-update-join-the-live-stream/ (03:29) - Blackmagic PYXIS 12K Camera Explained in Video Interview https://www.cined.com/blackmagic-pyxis-12k-camera-explained-in-video-interview/ (07:16) - Blackmagic PYXIS 12K Camera Price Increased by 32% to $6,595 in the USA Due to Tariffs https://www.cined.com/blackmagic-pyxis-12k-camera-price-increased-by-32-to-6595-in-the-usa-due-to-tariffs/  (10:57) - Immersive Video for Apple Vision Pro with Blackmagic Design URSA Cine Immersive & DaVinci Resolve 20 – Interview https://www.cined.com/immersive-video-for-apple-vision-pro-with-blackmagic-design-ursa-cine-immersive-davinci-resolve-20-interview/ (15:30) - Blackmagic Design PYXIS Top and Side Handles Explained https://www.cined.com/blackmagic-design-pyxis-top-and-side-handles-explained/ (19:27) - DaVinci Resolve 20 Released in Public Beta – with AI-Powered Features https://www.cined.com/davinci-resolve-20-released-in-public-beta-with-ai-powered-features/ (23:49) - FUJIFILM GFX ETERNA Camera Development Update – Internal ND, Hot Swap, Audio, and More https://www.cined.com/fujifilm-gfx-eterna-camera-development-update-internal-nd-hot-swap-audio-and-more/ (35:40) - Tilta Nucleus-M II Introduced – Features a New 4-Channel FIZ Unit, Flexible Motors, and More https://www.cined.com/tilta-nucleus-m-ii-introduced-new-fiz-unit-flexible-motors-and-more/ (40:04) - NiSi AUREUS PRIME T1.4 Cinema Lens Series Introduced – Fast & Full-Frame https://www.cined.com/nisi-aureus-prime-t1-4-cinema-lens-series-introduced-fast-amp-full-frame/ (44:31) - BLAZAR Mantis 1.33x Anamorphic Full-frame Lightweight Lens Series Announced https://www.cined.com/blazar-mantis-1-33x-anamorphic-full-frame-lightweight-lens-series-announced/ (46:57) - DZOFILM X-tract Macro Zoom Probe Lens Introduced – 3 versions, 18-28mm, T8, and Full-Frame https://www.cined.com/dzofilm-x-tract-macro-zoom-probe-lens-introduced-3-versions-18-28mm-t8-and-full-frame/ (49:25) - Laowa Probe Zoom Lenses Introduced – 15-35mm T12 / 15-24mm T8 with Interchangeable Barrel Options https://www.cined.com/laowa-probe-zoom-lenses-introduced-15-35mm-t12-15-24mm-t8-with-interchangeable-barrel-options/ (51:36) - Hollyland LARK MAX 2 – 32-bit Float and Wireless Monitoring https://www.cined.com/hollylands-lark-max-mk-ii/ (55:12) - Saramonic K9 Audio System Debuts with Ultra-Wide UHF Transmission https://www.cined.com/saramonic-k9-audio-system-debuts-with-ultra-wide-uhf-transmission/ (57:56) - Sennheiser Profile Wireless Introduced – All-In-One, Clip-On Microphone System https://www.cined.com/sennheiser-profile-wireless-introduced-all-in-one-clip-on-microphone-system/ (01:00:09) - NANLITE PavoTube II 6XR RGBWW Tubes with CRMX and 8 Pixels Explained https://www.cined.com/nanlite-pavotube-ii-6xr-rgbww-tubes-with-crmx-and-8-pixels-explained/ (01:01:35) - GVM Reign FH400 Introduced – Flat, Lightweight COB Light https://www.cined.com/gvm-reign-fh400-introduced-flat-lightweight-cob-light/ (01:03:17) - Aputure STORM XT52 – First Look at the Brightest LED Fixture Yet https://www.cined.com/aputure-storm-xt52-first-look-at-the-brightest-led-fixture-yet/ (01:05:45) - amaran Pano 120c Presented – a Lightweight, Full Color, LED Light Panel with Multiple Powering Options https://www.cined.com/amaran-pano-120c-presented-a-lightweight-full-color-led-light-panel-with-multiple-powering-options/ (01:08:35) - ASUS ProArt Monitors, a MicroLED Display, and a Display Calibrator Explained https://www.cined.com/asus-proart-monitors-a-microled-display-and-a-display-calibrator-explained/ (01:13:06) - ATOMOSphere, A-Eye PTZ cameras, a TX-RX System, and StudioSonic Headphones Introduced https://www.cined.com/atomos-atomosphere-a-eye-ptz-cameras-a-tx-rx-system-and-studiosonic-headphones-introduced/ (01:18:51) - Strada Agents Introduced – Be Your Own Cloud for Remote Collaboration https://www.cined.com/strada-agents-introduced-be-your-own-cloud-for-remote-collaboration/ We hope you enjoyed this episode! You have feedback, comments, or suggestions? Write us at podcast@cined.com

DJ Глюк - Жидкий Драм @ DJ Глюк 1. Peter Lix - Starwalk 2. Onism - Don't Hold Back 3. Duoscience - Facts 4. Jay Dubz - Garden Of Ecstasy 5. Bad 4 Life - Feel So Good 6. Bad 4 Life - Kiss Goodbye 7. Technimatic - From Within 8. Lsb, Etherwood - Evermade 9. Pyxis & Embers of Light - Growing 10. GLXY, Sâlo - Love Lost 11. Substainless - It Never Worked 12. Intelligent Manners, Command Strange - In My Mind 13. Shenji - Golden Glow 14. Pyxis & Heymac - High Enough 15. Pyxis & Blean - Time Travellers

durée : 00:44:34 - En pistes, contemporains ! du dimanche 06 avril 2025 - par : Emilie Munera - Dans votre émission de disques contemporains, retrouvez cette semaine de la nouveauté avec Philippe Quint, l'ensemble Pyxis et le Quatuor Girard. Découvrez aussi du plus ancien grâce à Edward Gardner. - réalisé par : Céline Parfenoff

durée : 00:44:34 - En pistes, contemporains ! du dimanche 06 avril 2025 - par : Emilie Munera - Dans votre émission de disques contemporains, retrouvez cette semaine de la nouveauté avec Philippe Quint, l'ensemble Pyxis et le Quatuor Girard. Découvrez aussi du plus ancien grâce à Edward Gardner. - réalisé par : Céline Parfenoff

durée : 00:44:34 - En pistes, contemporains ! du dimanche 06 avril 2025 - par : Emilie Munera - Dans votre émission de disques contemporains, retrouvez cette semaine de la nouveauté avec Philippe Quint, l'ensemble Pyxis et le Quatuor Girard. Découvrez aussi du plus ancien grâce à Edward Gardner. - réalisé par : Céline Parfenoff

Blackmagic leaks a 12K PYXIS camera just before NAB as the industry prepares for a major trade show. In this episode, hosts Addy Ghani and Joey Daoud dive into pre-NAB announcements, examining Strada's peer-to-peer media sharing tool, Adobe's new AI features, and how Gaussian splats are quietly becoming the next significant technology evolution. Plus, they unpack OpenAI's strategic move into open weights and what it means for enterprise AI adoption.

One link for those you've lost. One link for those you've found. And a link for yourself, to remember what ties you to those around you. We are nothing if not our bonds to each other.Content warnings for this episode include: betrayal // grief & loss // war // romance // blood // body horror // knives as weapons // harm to animals // threats of violence // assisted suicideGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Issilus, The Broken Sister, is Aabria Iyengar. The voice of Tharakus, Abyss in Chains, is Si Rutherford. This season's dramaturge is Tim Carlson. This episode was edited, scored, and produced by Si Rutherford. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

"Strategic planning is creating certainty in an uncertain world." – Tim Fulton Strategic planning is essential for success in any business, yet many companies either overlook or struggle with the process. In this episode, Trace Blackmore welcomes back Tim Fulton, President of Small Business Matters, to explore the fundamentals of strategic planning and how businesses can chart their course for success.   Tim shares insights on why strategic planning matters, how to involve the right people, and how to create a plan that actually works. Whether you're a business owner, manager, or part of a team, this episode provides valuable takeaways to help you navigate uncertainty, set clear objectives, and execute effectively. Why Strategic Planning is Critical Strategic planning helps businesses stay focused in an unpredictable world. By analyzing past performance, assessing the present, and setting future goals, companies can adapt to changing markets, industry trends, and emerging technologies like AI. Who Should Be Involved in Strategic Planning? Successful planning requires input from leaders and key employees at different levels. Involving the right people fosters collaboration, avoids blind spots, and ensures that the plan is practical and actionable, rather than created in isolation. The SWOT Analysis: A Tool for Understanding Your Business A SWOT analysis (Strengths, Weaknesses, Opportunities, and Threats) helps businesses understand their position. Identifying strengths and weaknesses within the company, along with external opportunities and threats, provides a clearer strategy for growth and risk management. Executing the Plan & Measuring Success A strategic plan is only effective if it's executed properly. Setting SMART goals (Specific, Measurable, Achievable, Relevant, Time-bound) ensures clarity, while quarterly reviews and color-coded tracking (Green, Yellow, Red) help teams monitor progress. Methods like the 12-Week Year and OKRs (Objectives & Key Results) keep businesses on track and accountable. Why Having a Third-Party Facilitator Can Make a Difference An outside facilitator brings an objective perspective, helping businesses stay focused and engaged during planning. Leaders who try to both facilitate and participate often struggle to balance these roles. Involving an expert improves discussions and strengthens team buy-in. Common Mistakes in Strategic Planning & How to Avoid Them Many businesses fail in strategic planning due to poor communication, lack of follow-through, and ignoring potential risks. A strong plan must be actively maintained throughout the year to ensure long-term success. Tim Fulton joined Trace Blackmore to deliver essential insights into strategic planning, emphasizing clarity, involvement, accountability, and the power of facilitation. This episode challenges listeners to create meaningful strategies, fostering organizational resilience and success in any environment. Stay engaged, keep learning, and continue scaling up your knowledge!   Timestamps    3:00 – Trace Blackmore encourages listeners to help spread the word about Scaling UP! H2O Podcast by sharing it with their colleagues and network 07:00 – Upcoming Events for Water Treatment Professionals 09:12 – Water You Know with James McDonald 11:00 – Interview starts: Welcoming back Tim Fulton 13:12 – What is Strategic Planning? 15:44 – Who should be involved in Strategic Planning? 23:22 – Why should companies strategically plan 34:58 – Best time for strategic planning 40:00 – Objective and Key Results (OKRs) explained   Quotes  "No weigh-in equals no buy-in.” - Patrick Lencioni, quoted by Trace “Fear is the biggest obstacle preventing businesses from strategic planning.” - Tim Fulton “Not having a plan is a plan for failure.” - Trace Blackmore “Doing strategic planning without a facilitator is like being quarterback and referee at the same time.” - Tim Fulton Connect with Tim Fulton Phone: (678) 427- 9436 Email: timfulton@hotmail.com Website: smallbusinessmattersonline.com LinkedIn: https://www.linkedin.com/in/timcfulton/  Click HERE to Download Episode's Discussion Guide     Guest Resources Mentioned The Meeting by Tim Fulton Measure What Matters by John Doerr Traction by Gino Wickman    Scaling UP! H2O Resources Mentioned AWT (Association of Water Technologies) Scaling UP! H2O Academy video courses Submit a Show Idea The Rising Tide Mastermind 022 The One with Tim Fulton   280 The One About Retaining Top Talent   289 The One About A SWOT Analysis with A Twist   368 Adapting to the New Workforce: Attracting Top Talent 164 The One With Chris McChesney What the Heck Is EOS? A Complete Guide for Employees in Companies Running on EOS by Gino Wickman   The 12 Week Year   The Five Dysfunctions of a Team by Patrick Lencioni Water You Know with James McDonald  Question: What do you call the attraction of water molecules to each other that gives water its unique properties, such as a high surface tension, high boiling point, and ability to dissolve many substances?   2025 Events for Water Professionals Check out our Scaling UP! H2O Events Calendar where we've listed every event Water Treaters should be aware of by clicking HERE.  

If you have a compass – physical or virtual – let it point you to the southeast as night falls for the constellation Pyxis – the celestial compass. It’s a short line of faint stars, aiming toward the remnants of the Argo – the ship that carried Jason and the Argonauts. In fact, Pyxis represents the Argo’s compass. You need a pretty dark sky to see even its brightest star. But that’s only because the star is about 900 light-years away. If you moved it to the distance of Sirius, the brightest star in the night sky, Alpha Pyxidis would outshine everything except the Sun and Moon. In astronomical parlance, Alpha Pyxis is “class B.” Astronomers classify stars by their surface temperature and color – hot stars are blue, while cool stars look orange or red. The hottest stars are class O, followed by class B. Alpha Pyx is tens of thousands of degrees hotter than the Sun, so it shines blue-white. The star is so hot because it’s more than 10 times as massive as the Sun. At that great mass, gravity squeezes the star tightly, making its interior intensely hot. As a result of those high temperatures, Alpha Pyxidis is “burning” through its hydrogen fuel in a hurry. So even though the star is less than one percent the age of the Sun, it’s already nearing the end of its life. Within a few million years, the star may go out with a bang: a titanic explosion known as a supernova. We’ll have more about Pyxis tomorrow. Script by Damond Benningfield

Your chains are rattling. The walls are crumbling. The Titans are coming, High Priestess... are you ready to do your duty to restore balance?  Content warnings for this episode include: betrayal // grief & loss // lies & concealment // body horror // corruption & possession // graphic violence // premeditated murder // blood // knives as weapons // harm to animals // self harm & allusions to suicide // religious overtones // war // fire // unsafe water // sexual undertones // Godkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Issilus, The Broken Sister, is Aabria Iyengar. The voice of Tharakus, Abyss in Chains, is Si Rutherford. This season's dramaturge is Tim Carlson. This episode was edited, scored, and produced by Si Rutherford. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

El sector de las tecnologías de la información necesita personal: se suele hablar de que en esta actividad existe desempleo negativo. Pero las oportunidades no son solo para los jóvenes que están saliendo del liceo y que se pueden enfocar a una carrera vinculada con este rubro. ¿Qué pasa con los mayores de 45 años, los que se quedaron sin trabajo a una edad en la que conseguir empleo de nuevo es más desafiante, o los que quieren simplemente cambiar de rumbo? Después de todo, ¿quién dice que uno tiene que atarse de por vida a un único sendero laboral? Pero, claro, la formación en un área como las TIC no es sencilla para alguien de mediana edad. Y quizás muchas empresas no se animan a tomar personas de ese segmento etario si ellas no tienen ya una trayectoria hecha. Por todo esto, en 2024 se lanzó Talento Tech +45, un programa financiado por Inefop e impulsado por las empresas Talento Senior Uruguay, Pyxis y Haltynea Consulting, que ya formó a 40 personas para reconvertirse en trabajadores TIC y que ahora está buscando sumar firmas“madrinas” para que se complete la inserción laboral. ¿Qué valor le dan al trabajo senior, tanto desde el punto de vista social como empresarial? ¿Por qué los mayores de 45 pueden aportarle valor a las empresas TI? ¿Y cómo lo ven los propios trabajadores “reconvertidos? Lo discutimos En Perspectiva en una nueva edición de La Mesa TIC junto a Ricardo Halty, director general de Haltynea Consulting; Carlos García, analista funcional en Pyxis y entró como parte del programa +50 de la empresa; Ivelise Reinaldo, cofundadora de Talento Senior Uruguay; y Alejandra Zepedeo, referente del programa Talento Tech +45 en Pyxis.

"If you're excellent at what you do, you've got to be paid like you're excellent." – Casey Brown  Ever wondered if you're truly getting paid what you're worth? In this unmissable episode of Scaling UP! H2O, we bring back Casey Brown, speaker, founder of Boost Pricing and author of the newly released Fearless Pricing. Known for her electrifying talks and actionable insights, Casey dives deep into how businesses can build confidence, charge their true value, and break free from the fear of pricing discussions.  From her journey as an engineer to becoming a pricing powerhouse, Casey's passion for helping businesses thrive shines through. Whether you're in sales, management, or leadership, this episode will leave you inspired and ready to tackle your next negotiation.   Highlights include:  The Psychology of Pricing: Why fear dominates most pricing conversations—and how to overcome it. Pricing Integrity: Learn how setting and sticking to fair, defensible prices can boost trust and long-term success. Handling Objections with Confidence: Proven strategies to turn pricing objections into opportunities. The "Hot Sauce" Analogy: Discover how to identify overlooked products or services that can deliver high profits with minimal pricing sensitivity. Unexercised Pricing Power: How to unlock hidden revenue by testing and refining your pricing strategy. Role-Playing for Success: How procedural memory and consistent practice can transform your sales team's confidence and results.  Bottom Line  This episode is your ultimate guide to fearless pricing, equipping you with the tools and mindset to boost profitability and set yourself apart from the competition. Don't miss the chance to learn from Casey's expertise and take your business to the next level!  Click play, take notes, and start commanding the value your business deserves. Don't let fear control your profits—listen now to gain the confidence and strategies you need to succeed. Stay engaged, keep learning, and continue scaling up your knowledge!    Timestamps    1:44 - Trace asks intriguing questions about the price of everyday items like gas and hot sauce to set the stage for a deeper discussion on pricing   02:23 - Events for Water Professionals   04:20 - Water You Know with James McDonald   05:35 - Interview with Casey Brown, speaker, founder of Boost Pricing, and the author of the newly released book ‘Fearless Pricing'   13:05 - How small discounts can devastate your bottom line  32:23 - Why debriefing every deal is critical for refining your pricing strategy  33:41 - The “Hot Sauce Analogy”  45:00 – Final Thoughts and Takeaways    Quotes  “We can't know, unless we try. The world is your Petri dish. “- Casey Brown  “The how is training and coaching and concepts; the why is rotted in the mission to help people who are excellent be paid like they're excellent.” - Casey Brown  “We can't fix pricing or profitability through calculation. We must address the biggest obstacle to success, which is FEAR.” - Casey Brown  “Pricing is generally the area of greatest fear and greatest discomfort.” - Casey Brown  “In absence of financial pricing integrity, unearned discounts hurt trust.” - Casey Brown  “The way to get comfortable doing something uncomfortable is to practice it.” - Casey Brown  "Every business has hot sauce and gasoline—products where pricing sensitivity varies drastically. Identify yours." – Casey Brown    Connect with Casey Brown  Phone: 614-679-7999  Email: casey@boostpricing.com   Website: www.Caseybrown.com    LinkedIn: https://www.linkedin.com/in/caseybrownboost/   Subscribe to Casey Brown's Newsletter: https://www.boostpricing.com/signup    Click HERE to Download Episode's Discussion Guide   Guest Resources Mentioned   Good to Great: Why Some Companies Make the Leap...And Others Don't by Jim Collins  They Ask You Answer by Marcus Sheridan  Outlive by Peter Attia  Essentialism by Greg McKeown  The Psychology of Money by Morgan Housel  Fearless Pricing by Casey Brown    Scaling UP! H2O Resources Mentioned  AWT (Association of Water Technologies)  Scaling UP! H2O Academy video courses  Submit a Show Idea  The Rising Tide Mastermind  363 Pricing Boost: Get Paid Well For Your Excellence with Casey Brown  The 7 Habits of Highly Effective People by Stephen R. Covey    Water You Know with James McDonald  Question: What is the conversion between parts-per-million and milligrams per Liter?   2025 Events for Water Professionals  Check out our Scaling UP! H2O Events Calendar where we've listed every event Water Treaters should be aware of by clicking HERE.

You don't want to look at it. You don't want to see. But you need to. The Weave has a story for you, and you need to look at it to know. But be careful... while you are watching, who is watching you?Content warnings for this episode include: grief & loss // betrayal // abandonment & rejection // death // corruption & possession // body horror // sleep paralysis // being watched // allusions to child endangerment // Godkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Issilus, The Broken Sister, is Aabria Iyengar. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs composed by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

What's inside you will sustain. What's inside you is a gift. What's inside you is a hope beyond hope. How do you slake your hunger? What would you give to feel whole again?Content warnings for this episode include: food & feeding // grief & loss // betrayal // threats // body horror // family conflict // discussion of attempted murderGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Ungal, The Undying is Matthew Mercer. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs composed by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Time. You thought you had more time. But between the Scion and the creeping form in the mirror, it has all come too fast. But goodness, aren't you hungry? Are you fed? Eat. Content warnings for this episode include: police brutality // premeditated violence // deceit // power dynamics // forced confinement // corruption // nepotism // hunger & forced feeding & food // being watched // body horror // murder Godkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Avaris Kerschel, The Scion of Perdition, is Brennan Lee Mulligan. The voice of Ungal, The Undying, is Matthew Mercer. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs composed by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Welcome to a monumental celebration in the world of Drum and Bass with The Stress Factor Podcast episode 320, marking a remarkable 15-year journey since its inception on January 1, 2010. This special episode is a thrilling 60 track studio mix by the renowned DJ B-12, designed to take listeners on an exhilarating auditory adventure. Spanning an impressive hour and 43 minutes, the mix showcases the finest in current upfront, liquid, and electro Drum and Bass, featuring euphoric vocals and stunning melodies that will resonate with both long time fans and newcomers alike. The energy is palpable, and the carefully curated selection of tracks promises to elevate your spirits and keep you moving, making it a perfect soundtrack for any occasion. As a heartfelt thank you to the loyal listeners who have supported The Stress Factor Podcast over the years, this episode is a testament to the community that has grown around it. Special acknowledgments go out to DJ Scottie B and Ste-J, who have been integral to the show since its early days, as well as DJ Tribo and R1 for their invaluable contributions. The episode features minimal talking, allowing the music to take center stage, but it does include a special voice message from the podcast's number one VIP listener, Axel The X Engler, adding a personal touch to this celebratory mix. With plans for a highly anticipated best of mix in February, the excitement continues as The Stress Factor Podcast looks forward to another 15 years of delivering the best in Drum and Bass. Big ups to all who have been part of this incredible journey! This episode contains tracks and remixes from the following artists and on the following labels Makoto, Lauren Archer, Liquicity Records, Nkz, Lizplay Records, Nicky Romero, Vikkstar, Alpharock, Oaks, Rameses B, Protocol Recordings, Genemo, YUNA, Saralia, Munix Records, Freaks Geeks, Flowidus, Gia Santho, Elevate Records, AL SO, Plasmator, Manifest, Andromedik, Lauren L'aimant, Akos Gyorfy, Kelle, Celsius Recordings, Friction, Circadian, Fallen State, Mathematica Records, Kleu, LoveThatBass, Receptor, Paperclip, Paperfunk Recordings, Voicians, Gentlemens Club, Lee Mvtthews, DnB Allstars, Marble Elephant, Monika, Spearhead Records, Cyazon, Gracie Van Brunt, Bassrush Records, K2T, DA TU, Offworld Recordings, Technimatic, Zara Kershaw, Keeno, Polaris, Keeno Music, Koven, AEON MODE, Monstercat, Modest Intentions, Formulus, Park Shadow, Straight Up Breakbeat, Rene Lavice, Felix Samuel, DeVice, Bloque, Blean, Interstellar Audio, S.P.Y, ALIBI, flowanastasia, Shogun Audio, Lexed, MAD1AD, Etherwood, UKF, InMost, Fae Vie, Telomic, DuoScience, Rezilient, Dux n Bass, EPITOME, LMX, Kubiks, Pyxis, Alpha Rhythm, Goldfat Records, Hybrid Minds, Lyvia, Melic, DistroKid, Close Inside, Dihanie, Ninkid, Perfect Pitch, Solar Vision, You Love Dance, Sam M, Ridmic, Jolliffe, Sydney Bryce, DrumAndBassArena, Lee Mvtthews, Kate McGill, DIMOD, BazAan, T And Sugah, Amber Jay, Feint, Maduk, Tengu, YosH, Artificial Intelligence, Genetics, Amber Jay, Holy Polly, NMA, Frameshift, Twintone, DNBB Digital, Wardown, Blu Mar Ten Music, Future Shock, Impact Music, Liquefaction, LW Recordings. Tracklist 01. Makoto Ft. Lauren Archer - Invincible [Liquicity Records] 02. Nkz - Bye Bye Darling [Lizplay Records] 03. Nicky Romero x Vikkstar x Alpharock x Oaks - Where Do I Go (Rameses B Extended Remix) [Protocol Recordings] 04. Genemo, YUNA and Saralia - Let Go (Goodbye) [Munix Records] 05. Freaks and Geeks, Flowidus and Gia Santho - Out My Head [Elevate Records] 06. ALSO and Plasmator - Open Your Eyes [Manifest] 07. Andromedik - Air (ft. Lauren L'aimant) [Andromedik] 08. Akos Gyorfy and Kelle - Bastard [Celsius Recordings] 09. Friction - Remember (Circadian Remix) [Elevate Records] 10. Fallen State - What You've Done [Mathematica Records] 11. Kleu - Fading Away (Dub Mix) [LoveThatBass] 12. Receptor and Paperclip - Long Story [Paperfunk Recordings] 13. Voicians - Back In Time [Liquicity Records 14. Receptor - Maybe You Could [Paperfunk Recordings] 15. Gentlemens Club and Lee Mvtthews - Frequency [DnB Allstars] 16. Marble Elephant - Melancholia [Celsius Recordings] 17. Fallen State - Open Mind [Mathematica Records] 18. Monika - Joanna [Spearhead Records] 19. Cyazon and Gracie Van Brunt - My Way Out [Bassrush Records] 20. K2T & DA TU - Unwavering Spirit [Offworld Recordings] 21. Technimatic - Only Dreamers (ft. Zara Kershaw) [Technimatic Music] 22. Keeno - Lights On (Polaris Remix) [Keeno Music] 23. Koven and AEON MODE - Polarised [Monstercat] 24. Modest Intentions and Formulus - Magnetize [Liquicity Records] 25. Park Shadow - Breach [Straight Up Breakbeat] 26. Andromedik - Time [Liquicity Records] 27. Rene Lavice ft. Felix Samuel - Count On You (Extended Mix) [DeVice] 28. Bloque and Blean - The Descent [Interstellar Audio] 29. S.P.Y x ALIBI x flowanastasia - This Is Goodbye [Shogun Audio] 30. Lexed, MAD1AD - It's Not Over [Manifest] 31. Etherwood - Sinking Sand [UKF] 32. Keeno x InMost x Fae Vie - To Feel OK Again (Telomic Remix) [Keeno Music] 33. DuoScience and Rezilient - Tread Lightly [Celsius Recordings] 34. Dux n Bass - Shootingstars [EPITOME] 35. Andromedik - Nothing Like You [Liquicity Records] 36. LMX and Kubiks - See Through [Liquicity Records] 37. Pyxis and Alpha Rhythm - Wanna Say Goodbye [Goldfat Records] 38. Hybrid Minds and Lyvia - Tear Drops [UKF] 39. Melic - Again [DistroKid] 40. Close Inside - Hybrolife [Dihanie] 41. Ninkid, Perfect Pitch and Solar Vision – The Power of Love [You Love Dance] 42. Marble Elephant - Carbon [Celsius Recordings] 43. Sam M - Close To The Edge [Ridmic] 44. Jolliffe and Sydney Bryce - Everything I Know [DrumAndBassArena] 45. Pyxis and Alpha Rhythm - Hummingberg [Goldfat Records] 46. Lee Mvtthews and Kate McGill - Take Me Anywhere [Elevate Records] 47. DIMOD and BazAan - Call Me [Lizplay Records] 48. T and Sugah - Euphoria (ft. Amber Jay) [Liquicity Records] 49. Scatterbrain and HumaNature - Second Thoughts (Subliminal Remix) [Fokuz Recordings] 50. Feint - Divided Sky [Liquicity Records] 51. Maduk - Stay Like This (Telomic Remix) [Liquicity Records] 52. Tengu x Emma Cannon - Coming Back To Me [YosH] 53. Artificial Intelligence and Makoto - Cold Expanse [Liquicity Records] 54. Genetics and Amber Jay - Escape [Ridmic] 55. Holy Polly - Breathe In [NMA] 56. Frameshift and Twintone - For Want Of You [DNBB Digital] 57. Wardown - And They Fell [Blu Mar Ten Music] 58. Future Shock - Alone Again [Impact Music] 59. Liquefaction - Tell Me [LW Recordings] 60. Wardown - No New Messages [Blu Mar Ten Music]

A prince amongst priests. A God amongst men. The darkness is your home, but be careful: what happens when the light is shone on your mortality?Content warnings for this episode include: shadows & the dark // nepotism // corruption // religious overtones // power dynamics // greed // uninvited entry // condescension // violence // premeditated murderGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Ashmedai is Cody Heath. The voice of Avaris Kerschel, The Scion of Perdition, is Brennan Lee Mulligan. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs composed by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

You have to run, you have to. You cannot fight the inevitable. And you have to remember that you can't fight the reality of what's right in front of you. What you see, what you know, and what you want. Content warnings for this episode include: grief // loss // death of a parent // parent-child conflict // gaslighting // being watched, pursed, & chased // burns & wounds // romance // heartbreak // threats of violence & persecution // systemic oppression and corruptionGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs composed by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Do you remember when you were made from the mud? How long have you been alone? Did your father want you? And who will save you when the Scion turns his gaze on you?Content warnings for this episode include: grief // loss // death of a parent // parent-child conflict // romance // heartbreak // threats of violence & persecution // systemic oppression and corruptionGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Davos Halassian is Christian Carlson. The voice of Avisan Eutoches is Tim Carlson. The voice of Ashmedai is Cody Heath. The voice of Avaris Kerschel, The Scion of Perdition is Brennan Lee Mulligan. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs composed by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

We reflect on the big news of the year and discuss some big stories and releases for each camera brand. Also, today's question is: do you touch the back screen of your mirrorless camera to set focus? New announcement: You can now support us on Patreon! The weekly show will be staying exactly the same, but if you want to contribute to our hosting costs for the podcast, we'd welcome your support. You can check it out here: https://www.patreon.com/cameragearpodcast Want to send us a question or comment, or just learn more about the show? Check out our website at https://cameragearpodcast.com, or email us directly at cameragearpodcast@gmail.com. Some links below to product sites are affiliate links and may result in a commission to the Camera Gear Podcast. Links: Canon Sigma Introduces Lenses for Canon RF Mount Canon R5 II Press Release We covered the Canon R5 II in episode 95 Fuji Fujifilm X100VI Press Release Fujifilm X-M5 Press Release We covered the X100VI in episode 74 We covered the X-M5 in episode 106 Leica Leica Q3 43 Leica D-Lux 8 We covered the Leica Q3 43 in episode 108 We covered the Leica D-Lux 8 in episode 92 Pixii Pixii Max We covered Pixii (although not this camera) in episode 49 Nikon / RED Nikon to Acquire US Cinema Camera Manufacturer RED Nikon Z6III Press Release We covered Nikon buying RED in episode 76 We covered the Nikon Z6III in episode 91 OM System OM-1 Mark II Press Release We covered the OM-1 Mark II in episode 77 Panasonic Panasonic S9 Press Release We covered the Panasonic S9 in episode 88 Pentax / Ricoh Pentax 17 Ricoh GRIII HDF We covered the Pentax 17 in episode 90 We covered the Ricoh GRIII HDF in episode 80 Sony Sony A9 III Press Release Sony A1 II Sony 28-70 f/2 GM We covered the Sony A9 III in episode 60 We covered the Sony A1 Ii in episode 113 We covered the Sony 28-70 f/2 in episode 113 Blackmagic Blackmagic Ursa Cine 12K Blackmagic Pyxis 6K We covered the Ursa Cine 12K and Pyxis in episode 84

Join us for an exclusive interview with the talented voice actress Mary Morgan! Known for her roles in hit series like Fairy Tail and Negima! Magister Negi Magi, Mary shares her journey into voice acting, behind-the-scenes stories, and insights into bringing beloved characters to life. Whether you're a fan of her work or curious about the art of voice acting, this conversation is packed with inspiration and fun. Don't forget to like, comment, and subscribe for more interviews with your favorite voice actors!Want to dive behind the scenes of voice acting? Check out this playlist filled with interviews from top voice actors talking about their experiences in anime, video games, and more: • Voices of the Industry ==============================Connect With Us!==============================TikTok: / movementradio IG: / movementradio3 BlueSky: https://bsky.app/profile/movementradi...Twitter/X: https://x.com/MovementRadio3Facebook: / movementradio2019 Threads: https://www.threads.net/@movementradio3==============================Subscribe & Listen to the Movement Radio Podcast!==============================YouTube: / @movementradio Apple: https://podcasts.apple.com/us/podcast...Spotify: https://open.spotify.com/show/3vfGZJD...

There is comfort in being lost. There is hope in being found. There is fear in being truly seen and known, but it is worth it in the end. Content warnings for this episode include: grief // loss // allusions to pre-meditated murder // parent-child conflict // betrayal // romance // heartbreakGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Peter Dickstein is a 35-year business leader (Founder, CEO, CFO, and strategy advisor). He is Founder of ShadyPower Technologies, developer of a proprietary, patent-pending IOT technology platform for climate-sustainable, enhanced comfort outdoor work and living. He is Co-Founder of TAPS, a machine-learning consultancy focused on sales lead optimization and churn prevention. He is Chairman (Emeritus) and Co-Founder of Solful (www.solful.com), a California-based branded destination cannabis dispensary company and a guest lecturer at universities including the Haas School of Business at UC Berkeley. He has served in CEO, Chairman, and other C-Suite roles for IOT, SAAS, cleantech, and travel insurance companies. In 1999 Peter founded and served as CEO of eProsper, Inc. (ultimately acquired by Morgan Stanley in 2018 for $900MM) whose patented, SAAS capitalization management system (“CapMx”) became the industry gold standard in the early 2000s and is used today by more than 6,000 venture-funded companies and their corporate law firms. Peter served as CFO for several medical device and technology companies including TruMed Systems, Inc., EndoTex Interventional Systems (acquired by Boston Scientific) and Atrionix (acquired by Johnson & Johnson). He was an EIR at Los Alamos National Laboratory where he identified and helped commercialize technology including Acoustic Cytometry Systems (acquired by Thermo Fisher Scientific) and architected the Los Alamos Venture Acceleration Fund. In the early 90s Peter negotiated a $500MM vendor financing facility for Pyxis Corporation (ultimately acquired by Becton Dickinson for $12BB) with GE Capital that rapidly accelerated Pyxis' market penetration and provided non-dilutive growth capital in lieu of equity. In addition to his general management roles, Peter has initiated, organized, negotiated, and completed numerous equity, debt, and M&A transactions with angel, institutional and strategic investors, and lenders. He has managed functional areas including product development and engineering, sales, service, finance and administration, and external relationships with investors, contract manufacturers, investment bankers, banks, attorneys, and auditors. Peter has served on the boards of Friends of the Urban Forest, the San Francisco Day School, and multiple companies. He is a dual citizen of the United States and Germany. He holds a B.A. from the University of Pennsylvania and a M.B.A. from The Wharton School.

It's time to stop dreaming, because the real world is banging on your door. The City of Glass demands your attention, as you look to find what's lost…Content warnings for this episode include: violence // body horror // police brutality // animal endangerment // death // murder // grief // loss // romance // heartbreak // being chased // ulterior motivesGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

We find Ever on her own journey through the Dreamscape, as she searches for answers about the path she and Rake now walk…Content warnings for this episode include: grief // romance // omission of truth // pain & superficial woundsGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

As Rake fails to dream, something else awaits in the liminal space between sleep and awake…Content warnings for this episode include: Sleep paralysis // Body horror // creature horror & teeth // threats of violence Godkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Dr. Ryan Augustin and Dr. Jason Luke discuss neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, promising new TIL therapy for advanced melanoma, and the emerging role of CD3 engagers in treatment strategies. TRANSCRIPT Dr. Ryan Augustin: Hello, I'm Dr. Ryan Augustin, your guest host of the ASCO Daily News Podcast today. I'm a medical oncology fellow at Mayo Clinic in Rochester, Minnesota. Joining me today is Dr. Jason Luke, an associate professor of medicine and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center. I had the privilege of working as a postdoc in Jason's translational bioinformatics lab, where we investigated mechanisms of resistance to immunotherapy in melanoma and other cancers.  Today, we'll be discussing 3 important topics, including neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, the impact and practical considerations for incorporating TIL therapy into melanoma, and the current and future use of CD3 engagers in both uveal and cutaneous melanoma.  You'll find our full disclosures in the transcript of this episode.  Jason, it's great to have this opportunity to speak with you today. Dr. Jason Luke: Absolutely. Thanks, Ryan. It's great to see you. Dr. Ryan Augustin: So, to kick things off, Jason, we, of course, have seen tremendous advances in cancer immunotherapy, not only in metastatic disease but also the perioperative setting. Recent data have shown that the use of neoadjuvant therapy can provide not only critical prognostic information but can also help individualize post-resection treatment strategies and potentially even eliminate adjuvant therapy altogether in patients who achieve a pathologic, complete response. This signifies a conceptual shift in oncology with the goal of curing patients with immunotherapy. In triple-negative breast cancer, the KEYNOTE-522 regimen with pembrolizumab is standard of care. In non-small cell lung cancer, there are now four FDA approved chemo-IO regimens in both the neoadjuvant and perioperative settings. And, of course, in melanoma, starting with SWOG S1801 utilizing pembro mono therapy, and now with combined CTLA-4 PD-1 blockade based on results from the NADINA trial, neoadjuvant IO is the new standard of care in high-risk, resectable melanoma. It's important to highlight this because whereas other tumor types have more mature multidisciplinary care, for example, patients with breast cancer are reviewed by the whole team in every center, and every patient with lung cancer certainly benefits from multidisciplinary care conferences, that's not always the case with melanoma, given the relative frequency of cases compared to other tumor types.  Jason, would you say that we have now moved into an era where the integration of a multidisciplinary team and melanoma needs to be prioritized. And why is it important to have multidisciplinary team coordination from the onset of a patient's diagnosis? Dr. Jason Luke: Well, I think those are great questions, Ryan, and I think they really speak to the movement in our field and the great success that we've had integrating systemic therapy, particularly immunotherapy, into our treatment paradigms. And so, before answering your question directly, I would add even a little bit more color, which is to note that over the last few years, we've additionally seen the development of adjuvant therapy into stages of melanoma that, historically speaking, were considered low-risk, and medical oncologists might not even see the patient. To that, I'm speaking specifically about the stage 2B and 2C approvals for adjuvant anti-PD-1 with pembrolizumab or nivolumab. So this has been an emerging complication.  Classically, patients are diagnosed with melanoma by either their primary care doctor or a dermatologist. Again, classically, the next step was referral to a surgeon who had removed the primary lesion, with discussion around nodal evaluation as well. And that paradigm has really changed now, where I think integration of medical oncology input early on in the evaluation of the appropriate treatment plan for patients with melanoma is quite a pressing issue now, both because we have FDA approvals for therapeutics that can reduce risk of recurrence, and whether or not to pursue those makes a big difference to the patient for discussion early on.  And, moreover, the use of systemic therapies now, prior to surgery, of course, then, of course, requires the involvement of medical oncology. And just for an emphasis point on this, it's classically the case, for good reason, that surgeons complete their surgery and then feel confident to tell the patient, “Well, we got it all, and you're just in really good shape.” And while I understand where that's coming from, that often leaves aside the risk of recurrence. So you can have the most perfect surgery in the world and yet still be at very high risk of recurrence. And so it's commonly the case that we get patients referred to us after surgery who think they're just in totally good shape, quite surprised to find out that, in fact, they might have a 20% to 50% risk of recurrence. And so that's where this multidisciplinary integration for patient management really does make a big difference.  And so I would really emphasize the point you were making before, which is that we need multidisciplinary teams of med onc with derm, with surgery early on, to discuss “What are the treatment plans going to be for patients?” And that's true for neoadjuvant therapy, so, for palpable stage 3, where we might give checkpoint inhibitors or combinations before surgery. But it's true even in any reasonably high-risk melanoma, and I would argue in that state, anything more than stage 1 should be discussed as a group, because that communication strategy with the patient is so important from first principles, so that they have an expectation of what it's going to look like as they are followed out over time. And so we're emphasizing this point because I think it's mostly the case at most hospitals that there isn't a cutaneous oncology disease management meeting, and I think there needs to be.  It's important to point out that usually the surgeons that do this kind of surgery are actually either the GI surgeons who do colon cancer or the breast surgeons. And so, given that melanoma, it's not the most common kind of cancer, it could easily be integrated into the existing disease review groups to review these cases. And I think that's the point we really want to emphasize now. I think we're not going to belabor the data so much, but there are enormous advantages to either perioperative or adjuvant systemic therapy in melanoma. We're talking about risk reduction of more than 50%, 50-75% risk reduction. It's essential that we make sure we optimally offer that to patients. And, of course, patients will choose what they think is best for their care. But we need to message to them in a way that they can understand what the risks and benefits of those treatments are and then are well set up to understand what that treatment might look like and what their expectations would be out over time.  So I think this is a great art of medicine place to start. Instead of belaboring just the details of the trial to say, let's think about how we take care of our patients and how we communicate with them on first principles so that we can make the most out of the treatments that we do have available. Dr. Ryan Augustin: That's great, Jason. Very insightful points. Thank you.  So, shifting gears now, I'd also like to ask you a little bit about TIL therapy in melanoma. So our listeners will be aware that TIL is a promising new approach for treating advanced melanoma and leverages the power of a patient's cytotoxic T cells to attack cancer cells. While we've known about the potential of this therapy for some time, based on pioneering work at the NCI, this therapy is now FDA approved under the brand AMTAGVI (Lifileucel) from Iovance Biotherapeutics, making it the first cellular therapy to be approved for a solid tumor. Now, I know TIL therapy has been administered at your institution, Jason, for several years now, under trial status primarily for uveal melanoma using an in-house processing. But for many cancer centers, the only experience with cellular therapy has come under the domain of malignant hematology with CAR T administration. At our institution, for example, we have only recently started administering TIL therapy for melanoma, which has required a tremendous multidisciplinary effort among outpatient oncology, critical care, and an inpatient hematology service that has expertise in cytokine release syndrome.  Jason, where do you see TIL therapy fitting into the metastatic space? Which patients do you think are truly candidates for this intensive therapy? And what other practical or logistical considerations do you think we should keep in mind moving forward? Dr. Jason Luke: Well, thanks for raising this. I think the approval of lifileucel, which is the scientific name for the TIL product that's on the market now. It really is a shift, a landscape shift in oncology, and we're starting in melanoma again, as seems to be commonly the case in drug development. But it's really important to understand that this is a conceptually different kind of treatment, and therefore, it does require different considerations. Starting first with data and then actualization, maybe secondarily, when we see across the accelerated approval package that led to this being available, we quote patients that the response rate is likely in the range of 30%, maybe slightly lower than that, but a meaningful 25% to 30% response rate, and that most of those patients that do have response, it seems to be quite durable, meaning patients have been followed up to four years, and almost all the responders are still in response. And that's a really powerful thing to be able to tell a patient, particularly if the patient has already proceeded through multiple lines of prior standard therapy. So this is a very, very promising therapy.  Now, it is a complicated therapy as well. And so you highlighted that to do this, you have to have a tumor that's amenable for resection, a multidisciplinary team that has done a surgery to remove the tumor, sent it off to the company. They then need to process the TIL out of the tumor and then build them up into a personalized cell product, bring it back, you have to lympho-deplete the patient, re-introduce this TIL. So this is a process that, in the standard of care setting under best circumstances, takes roughly six weeks. So how to get that done in a timely fashion, I think, is evolving within our paradigms. But I think it is very important for people who practice in settings where this isn't already available to realize that referring patients for this should be a strong consideration. And thinking about how you could build your multidisciplinary team in a way to be able to facilitate this process, I think is going to be important, because this concept of TIL is relevant to other solid tumors as well. It's not approved yet in others, but we kind of assume eventually it probably will be. And so I think, thinking through this, how could it work, how do you refer patients is very important.  Now, coming back to the science, who should we treat with this? Well, of course, it's now an air quotes “standard of care option”, so really it ought to be available to anybody. I will note that currently, the capacity across the country to make these products is not really adequate to treat all the patients that we'd want. But who would we optimally want to treat, of course, would be people who have retained a good performance status after first line therapy, people who have tumors that are easily removable and who have not manifested a really rapid disease progression course, because then, of course, that six-week timeline probably doesn't make sense. The other really interesting data point out of the clinical trials so far is it has looked like the patients who got the least amount of benefit from anti-PD-1 immunotherapy, in other words, who progressed immediately without any kind of sustained response, those patients seem to have the best response to TILs, and that's actually sort of a great biomarker. So, this drug works the best for the population of patients where checkpoint inhibitors were not effective. And so as you think about who those patients might be in your practice, as you're listening, I think prioritizing it for primary progression on anti PD-1, again and giving it ahead thought about how would you get the patient through this process or referred to this process very quickly is really important because that lag time is a problem. Patients who have melanoma tend to progress reasonably quickly, and six weeks can be a long time in melanoma land. So, thinking ahead and building those processes is going to be important moving into the future Dr. Ryan Augustin: Definitely appreciate those practical considerations. Jason, thank you.  Moving on to our final topic, I was hoping to discuss the use of immune cell engagers in melanoma. So, similar to CAR T therapy, bispecific T-cell engagers, or BiTEs, as they're commonly known, are standard of care in refractory myeloma and lymphoma. But these antibodies engaging CD-3 on T cells and a tumor specific antigen on cancer cells are relatively new in the solid tumor space. Tarlatamab, which is a DLL-3 and CD-3 bispecific antibody, was recently approved in refractory small cell lung cancer, and, of course, tebentafusp, an HLA-directed CD-3 T cell engager was approved in uveal melanoma in 2022. Both T and NK cell engaging therapies are now offering hope in cancers where there has historically been little to offer. However, similar to our discussion with TIL therapy, bispecifics can lead to CRS and neurotoxicity, which require considerable logistical support and care coordination.  Jason, I was wondering if you could briefly discuss the current landscape of immune cell engagers in melanoma and how soon we may see these therapies enter the treatment paradigm for cutaneous disease. Dr. Jason Luke: I think it is an exciting, novel treatment strategy that I think we will only see emerge more and more. You alluded to the approval of tebentafusp in uveal melanoma, and those trials were, over the course of a decade, where those of us in solid tumor land learned how to manage cytokine release syndrome or the impact of these C3 bispecifics, in a way that we weren't used to. And what I'll caution people is that CRS, as this term, it sounds very scary because people have heard of patients that, of course, had difficult outcomes and hematological malignancies, but it's a spectrum of side effects. And so, when we think about tebentafusp, which is the approved molecule, really what we see is a lot of rash because GP100, the other tumor antigen target, is in the skin. So, patients get a rash, and then people do get fevers, but it's pretty rare to get more than that. So really what you have to have is the capacity to monitor patients for 12 hours, but it's really not more scary than that. So it really just requires treating a few people to kind of get used to these kinds of symptoms, because they're not the full-on ICU level CRS that we see with, say, CAR T-cells.  But where is the field going? Well, there's a second CD3 bispecific called brenetafusp that targets the molecule PRAME, that's in a phase 3 clinical trial now for frontline cutaneous melanoma. And tebentafusp is also being evaluated in cutaneous melanoma for refractory disease. So, it's very possible that these could be very commonly used for cutaneous melanoma, moving into, say, a two-to-four-year time horizon. And so therefore, getting used to what are these side effects, how do you manage them in an ambulatory practice for solid tumor, etc., is going to be something everyone's going to have to learn how to deal with, but I don't think it should be something that people should be afraid of.  One thing that we've seen with these molecules so far is that their kinetics of treatment effect do look slightly different than what we see with more classic oncology therapies. These drugs have a long-term benefit but doesn't always manifest as disease regression. So, we commonly see patients will have stable disease, meaning their tumor stops growing, but we don't see that it shrank a lot, but that can turn into a very meaningful long-term benefit. So that's something that we're also, as a community, going to have to get used to. It may not be the case we see tumors shrink dramatically upfront, but rather we can actually follow people with good quality- of-life over a longer period of time.  Where is the field going? You mentioned tarlatamab in small cell lung cancer, and I think we're only going to see more of these as appropriate tumor antigens are identified in different tumors. And then the other piece is these CD3 engagers generally rely upon some kind of engagement with a T cell, whether CD3 engagers, and so they can be TCR or T-cell receptor-based therapies, although they can be also SCFV-based. But that then requires new biomarkers, because TCR therapy requires HLA restriction. So, understanding that now we're going to need to profile patients based on their germline in addition to the genomics of the tumor. And those two things are separate. But I would argue at this point, basically everybody with cutaneous melanoma should be being profiled for HLA-A(*)0201, which is the major T-cell receptor HLA haplotype that we would be looking for, because whether or not you can get access immediately to tebentafusp, but therefore clinical trials will become more and more important.  Finally, in that T-cell receptor vein, there are also T cell receptor-transduced T cells, which are also becoming of relevance in the oncology community and people listening will be aware in synovial sarcoma of the first approval for a TCR-transduced T cell with afamitresgene autoleucel. And in melanoma, we similarly have TCR-transduced T cells that are coming forward in clinical trials into phase 3, the IMA203 PRAME-directed molecule particularly. And leveraging our prior conversation about TILs, we're going to have more and more cellular based therapies coming forward, which is going to make it important to understand what are the biomarkers that go with those, what are the side effect profiles of these, and how do you build your practice in a way that you can optimally get your patients access to all of these different treatments, because it will become more logistically complicated, kind of as more of these therapies come online over the next, like we said, two to four years kind of time horizon. So, it's very exciting, but there is more to do, both logistically and scientifically. Dr. Ryan Augustin: That's excellent. Thanks, Jason, and thank you so much for sharing your great insight with us today on the ASCO Daily News Podcast. Dr. Jason Luke: Thanks so much for the opportunity. Dr. Ryan Augustin: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode, and you can follow Dr. Luke on X, formerly known as Twitter, @jasonlukemd. And you can find me, @RyanAugustinMD. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers: @ryanaugustinmd Dr. Jason Luke @jasonlukemd   Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Ryan Augustin: No relationships to disclose Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Ever and Rake meet at the Lamp. The glint of the blade, the draw of power. Deals struck, bargains made. You're ready, right?Content warnings for this episode include: Threats of violence // anger // concealed identity // knives as weapons // gaslighting // substance useGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Episode 239: What hidden insights can customer behavior data analysis reveal about how successful one food delivery app may be over another? Discover how analysis of externally sourced customer behavior data can fuel dramatic improvements in revenue forecasts and strategic decisions. See how competitor data analysis can help identify strengths and weaknesses that are otherwise hidden. In this episode of Customer Confidential, we're joined by Dan McCarthy, director and co-founder of Theta and Associate Professor of Marketing at the University of Maryland's Robert H. Smith School of Business. Dan shares findings from Theta and Bain & Company's jointly published consumer purchase data study, “Customer Lifetime Value across Food Delivery Competitors.” Together, Dan and Rob explore how they used a proprietary database of credit card transaction data from Pyxis to track customer behavior for subscription services over five years. They describe how accounting for corresponding economic factors like seasonality and the Covid-19 pandemic helped improve forecasts of transaction velocity, spending, and retention. Learn which food delivery app had the best customer loyalty, the most customers, and highest per-customer spending. Guest: Dan McCarthy, Director and Co-Founder of Theta, Associate Professor of Marketing at the University of Maryland, College Park Host: Rob Markey, Partner, Bain & Company Give Us Feedback: We'd love to hear from you. Help us enhance your podcast experience by providing feedback here in our listener survey. Want to get in touch? Send a note to host Rob Markey here. Time-Stamped List of Topics Covered: [02:00] Introduction to customer behavior analysis and business forecasting [05:15] How companies can use historical data to predict customer lifetime value [10:00] Insights from customer data and the role of subscription services [15:30] The impact of external factors like economic shifts and market changes on consumer behavior [20:00] How businesses can improve acquisition and retention strategies using data [25:00] Using customer lifetime value to forecast future revenue and business growth Time-Stamped Notable Quotes: [02:45] “The notion of having a consistent data set with multiple companies in it so you can compare … all these different food delivery companies [means] you can explicitly see them and you can see the same consumers buying across them.” [05:37] “It's primarily taking these different vintages of customers—where a vintage is defined by, ‘When did that customer make their very first purchase with your firm?'—and then within that vintage, what we want to explain is what these individual customers are going to do in the future.” [07:42] “[The data] is what allows us to say things like, is this company acquiring customers well? Are they retaining customers well? How frequently are they buying? And how does that compare across different companies?” Additional Resources: Customer Lifetime Value across Food Delivery Competitors Pyxis by Bain & Company

Hello and welcome to The Stress Factor Drum and Bass Podcast episode 315, featuring the highly anticipated return of DJ B-12. This episode presents an extraordinary 100 Track super mix that encapsulates the essence of contemporary drum and bass, showcasing the genre's most exhilarating and cutting edge tracks. Listeners can expect a rich tapestry of sound, characterized by stunning vocals, emotive breakdowns, and a blend of darker, edgier elements that add depth to the mix. The infusion of trancey and electro influences further elevates the listening experience, making this episode a must listen for enthusiasts of high energy music. We invite you to immerse yourself in this remarkable auditory journey and share the excitement with fellow music lovers. This episode includes tunes and remixes from the following artists and labels DC Breaks, Viper Recordings, Metrik, Insomniac Music Group, Houndeye, Delta Heavy, Grafix, Hospital Records, Lexurus, Polygon, Liquicity, ShockOne, Dark Machine Recs, SiLi, Lauren Laimant, Dualistic, Koven, A.M.C, UKF, Aktive, Maduk, Crooked Bangs, Fred V, 1991, Alex Hosking, Chaos, Madface, Dawn Wall, Anni, Bungle, Scientific, Itro, Slippy, Josh Rubin, NCS, Sola, Pyxis, Dirtbox Recordings, Zero T, The North Quarter, Hazey, Ponz, Hiraeth, Prospex, Audio Overload Jungle Records, Fourward, Elevate Record, High Contrast, Highly Contrasting, Seba, Phil Tangent, Secret Operations, Wyld Dogz, Sharlene Hector, Nero, Create Music Group, Andy C, Becky Hill, Polydor Records, Andromedik, Nu-La, Malaky, Galacy Records, DJ Phantasy, Nicky Blackmarket, Lords Of Rave, Sweet Female Attitude, Lords of Moondance, L-Side, NUFORM, Low Steppa, Kelli-Leigh, Shapes, Armada Music, Polaris, Innerground Records, Bastion, Fade Black, Leo Law, Pilot., Skepsis, Brodie, FFRR, Critical Music, Jon Void, Kastuvas, Gas Pedal, Leony, Sigma, Kontor Records, Voicians, Krakota, Lee Mvtthews, Sleepless Music Ltd., Minos, Fokuz Recordings, Drumsound & Bassline Smith, Technique Recordings, Neuron, Celsius Recordings, 3Beat, Sub Focus, Pola & Bryson, EMI, McLean, Camo & Krooked, Asylum Records, Disciples, Delilah, MONSS, Ministry of Sound Recordings, Georgie Riot, Spaven, Riot Record, Hiraeth, Grum, Natalie Shay, Grafix, Anjunabeats, Eviya, Sonny Fodera, blythe, SOLOTOKO, Dogzone Records, Outerbass, Fokuz Recordings, ZeroZero, Riya, Flexout Audio, Virtue, xJAK Audio, Brookes Brothers, Mia Kirkland, The Prototypes, Lowes, Danny Byrd, S.P.Y., CmdCtrl, DnB Allstars, Jazmine Johnson, James Hiraeth, Insanity Records, Iklektix, Beta Recordings, Cauzer, Matrix, Futurebound, Blaine Stranger, Tom Cane, Rex Hooligan, Chrissie Huntley, Camelphat, Sony Music Entertainment UK, Artificial Intelligence, Artino, Flux Pavilion, Matthew Koma, Circus, Oliver Tree, Atlantic Records, Arielle Free, GHSTGHSTGHST, Flava D, Telomic, Dimension, Alison Wonderland, SOLR, GEST, Shogun Audio, Moore Kismet, Rameses B, Monstercat, Rhode, Chicane, Bryan Adams, Monika, Spearhead Records, AR CO, ARTY, Etherwood, Jay Sorrow, Aluna, Picard Brothers, Kaleena Zanders, DRIIA, Mad Decent, SACHI, Kanine, Casablanca Records, Republic Records. Tracklist 01. DC Breaks - Exoplanet [Viper Recordings] 02. Metrik - Immortal [Insomniac Music Group] 03. Houndeye - Falling Awake [Viper Recordings] 04. Delta Heavy - Midnight Forever [Delta Heavy] 05. Grafix - Skyline (ft. Metrik) [Hospital Records] 06. Lexurus and Polygon - Waveline [Liquicity] 07. Polygon - Feel This Good [Liquicity] 08. ShockOne - Follow Me [Dark Machine Recs] 09. SiLi - TRONCE [Liquicity] 10. Delta Heavy - Sanctuary (ft. Lauren Laimant) [Delta Heavy] 11. Dualistic - Cluster Patrol [Liquicity] 12. Koven and A.M.C - Hooked [UKF] 13. Aktive - Loko [UKF] 14. Maduk and Lexurus - Follow My Heart (ft. Crooked Bangs) [UKF] 15. Fred V - Luminous [Hospital Records] 16. 1991 - Jungle (ft. Alex Hosking) [Chaos] 17. Madface - Paralyzed [Viper Recordings] 18. Dawn Wall - Sinner (ft. Anni)[UKF] 19. Bungle - Arise [Scientific] 20. Itro - Promises [Liquicity] 21. Slippy and Josh Rubin - Crash (Extended) [NCS] 22. Sola and Pyxis - Time Lost [Dirtbox Recordings] 23. Zero T - Don't Know [The North Quarter] 24. Hazey and Ponz - Go Under [Liquicity] 25. Hiraeth - Deep Blue [Liquicity] 26. Prospex - Without You [Audio Overload Jungle Records] 27. Fourward - Show Me Love [Elevate Records] 28. High Contrast - Remember Me [Highly Contrasting] 29. Seba - Eztli (Phil Tangent remix) [Secret Operations] 30. Wyld Dogz - Lola's Theme (feat. Sharlene Hector) (Extended Mix) [Dogzone Records] 31. Nero - The Unknown [Create Music Group] 32. Andy C x Becky Hill - Indestructible (Extended Mix) [Polydor Records] 33. Andromedik and Lexurus - Adrenaline (feat. Nu-La) [Liquicity] 34. Malaky and pyxis - Nimbus [Galacy Records] 35. Delta Heavy - No Gravity [Delta Heavy] 36. DJ Phantasy x Nicky Blackmarket x Lords Of Rave - Say Yes (feat. Sweet Female Attitude)[Lords of Moondance] 37. L-Side - Regret [NUFORM] 38. Low Steppa - Runnin' feat. Kelli-Leigh (Shapes Extended Remix) [Armada Music] 39. Polaris - One More Time [Innerground Records] 40. Bastion and Fade Black - Blood and Gold (ft. Leo Law) [Pilot.] 41. Skepsis and Brodie - Double Vision (Extended) [FFRR] 42. Fade Black - Elysium [Critical Music] 43. Jon Void - LFG [Liquicity] 44. Kastuvas - Tell Me Why [Gas Pedal] 45. Leony - Remedy (Sigma Extended Remix) [Kontor Records] 46. Voicians - Lost At Sea [Liquicity Records] 47. Krakota and Lee Mvtthews - Feel Good [Sleepless Music Ltd.] 48. Minos - Mystic Vibez [Fokuz Recordings] 49. 1991 Ft. Mugatu - Cyclone [Chaos] 50. Drumsound and Bassline Smith - One More Time [Technique Recordings] 51. Neuron - Always Together [Celsius Recordings] 52. Sigma - That Feeling [3Beat] 53. Sub Focus and Pola and Bryson - Waiting VIP (ft. Kelli Leigh) [EMI] 54. McLean - Finally In Love (Camo and Krooked Remix) [Asylum Records] 55. Lexurus - Take Me Away [Liquicity] 56. Disciples x Delilah - If I Stay (MONSS Remix) [Ministry of Sound Recordings] 57. Georgie Riot and Spaven - Out Of My Mind [Riot Records] 58. Hiraeth - Origins (SiLi Remix) [Liquicity] 59. Grum ft. Natalie Shay - Don't Look Down (Grafix Remix) [Anjunabeats] 60. Lexurus and Itro - Letting Go (feat. Eviya) [Liquicity] 61. Sonny Fodera - Mind Still (feat. blythe) (1991 Remix) [SOLOTOKO] 62. Wyld Dogz - Spaceman [Dogzone Records] 63. Outerbass - Radical [Fokuz Recordings] 64. ZeroZero and Riya - Thinking Over It [Flexout Audio] 65. Virtue - Second Guessing [xJAK Audio] 66. Brookes Brothers, Mia Kirkland - Enemies [UKF] 67. The Prototypes - Reason (feat. Lowes) (Danny Byrd Extended Remix) [The Prototypes] 68. Danny Byrd, S.P.Y. and Cmd Ctrl - Pink Champagne [DnB Allstars] 69. Delta Heavy - Chasing Gold (ft. Jazmine Johnson) [Delta Heavy] 70. James Hiraeth - Chasing Highs (Slow Motion) (Extended) [Insanity Records] 71. Iklektix - How I Like It [Beta Recordings] 72. Fade Black - Condemned (Cauzer Remix) [Critical Music] 73. Matrix and Futurebound and Blaine Stranger - New Energy (ft. Tom Cane) [Viper Recordings] 74. Rex Hooligan - Save Me (feat. Chrissie Huntley) [Liquicity] 75. Camelphat - Easier ft. LOWES (Sub Focus Remix) [Sony Music Entertainment UK] 76. Voicians - Keep Me Under [Liquicity] 77. Artificial Intelligence - Even Though [Liquicity] 78. Neuron - No More [Celsius Recordings] 79. Artino - What I Want [Liquicity] 80. Flux Pavilion x Matthew Koma - Emotional (James Hiraeth Remix) [Circus] 81. Outer Bass - Stardrop [Fokuz Recordings] 82. Oliver Tree - Miss You (Georgie Riot Remix) [Atlantic Records] 83. Arielle Free and GHSTGHSTGHST - Blow My Mind (Flava D Extended Remix) [Armada Music] 84. Voicians and Telomic - Eternalize [Liquicity] 85. Dimension and Alison Wonderland - Satellite [Dimension] 86. Neuron - Searching [Celsius Recordings] 87. Fade Black - Far Gone [Critical Music] 88. SOLR - Your Love [Celsius Recordings] 89. Delta Heavy - High On You [Delta Heavy] 90. GEST - Brutalis [Shogun Audio] 91. Moore Kismet - Overthinking Out Loud [UKF] 92. Rameses B - Children [Monstercat] 93. Voicians and Rhode - Never Go Back [Liquicity] 94. Fade Black - Sane feat. Leo Law [Critical Music] 95. Chicane - Don't Give Up feat. Bryan Adams (Grafix Extended Remix) [Armada Music] 96. Monika - Death Blinding [Spearhead Records] 97. Sub Focus - Vibration (One More Time) (Visualiser) ft. AR/CO [EMI] 98. ARTY and Etherwood - In My Head feat. Jay Sorrow (Extended Mix) [Armada Music] 99. Aluna, Picard Brothers and Kaleena Zanders - Supernova (DRIIA Remix) [Mad Decent] 100.SACHI - Take Me Back (Kanine Remix) [Casablanca Records (Republic Records)]

Discover Breakthroughs in Sunflower Oil Wastewater Treatment: A Special Re-Air of Our Most Popular Episode from 2023 When it comes to oil wastewater treatment, the challenges can feel overwhelming. But what if there was a way to tackle these obstacles with cutting-edge solutions? In this special re-airing of our most popular episode from 2023, Swati Sharma, Ph.D. an expert at Water Engineering Inc. (WEI), walks us through her innovative research that's helping water treaters around the world. Her expertise is backed by groundbreaking research, including her thesis titled "How to Estimate the Best Treatment Conditions for Sunflower Oil Wastewater Using Advanced Electrooxidation Process", which she graciously shares with our global audience. Gain insights into electrooxidation processes and valuable advice for aspiring water treatment researchers. Even if you've heard this episode before, we promise you'll learn something new this time around. Dr. Sharma's expertise in electrooxidation processes and her passion for solving complex wastewater problems is sure to inspire and equip you to approach your next challenge with confidence. What makes treating sunflower oil wastewater so difficult? Sunflower oil wastewater is particularly challenging because it contains high levels of organic pollutants. Traditional methods often fall short, leaving treaters frustrated and looking for better solutions. But as Dr. Sharma shares, every wastewater is different, and each treatment process behaves uniquely depending on the specific characteristics. “I found that each wastewater was so different in its characteristics, that each of these treatments behaved completely differently. Electrocoagulation (EC) was really good with the canola oil, whereas I found that Electrooxidation (EO) was a better process for sugar beets, which are really high in organic loading.” – Dr. Swati Sharma How does electrooxidation make a difference? Dr. Sharma explains that advanced processes like electrooxidation and electrocoagulation offer more precise control over treating specific types of wastewaters. Electrooxidation, for instance, can target and break down organic pollutants more effectively than conventional methods, making it a game-changer for sunflower oil wastewater. “Wastewater is like math, it's like a game. You have to understand it and enjoy doing it. It's a puzzle, you need to connect the dots to make a beautiful picture.” – Dr. Swati Sharma What advice does Dr. Sharma have for aspiring researchers? Dr. Sharma's path to success wasn't without challenges. In the episode, she offers valuable insights into the importance of persistence and curiosity. Whether you're a seasoned professional or just starting out, her advice applies across the board. “Sometimes your hypothesis doesn't match your findings and it's hard. You dedicate so many hours of your life to your study and you are so passionate about this, and it's demotivating at times. But you have to learn what has failed and why it has failed. Find the reason behind your failure and it will lead to your success. That's what I believe in.” – Dr. Swati Sharma What's the key to successful wastewater treatment? Understanding the specific characteristics of the wastewater you're dealing with is essential to finding the right solution. Dr. Sharma emphasizes that it's not just about adding chemicals but truly understanding the problem. “It's not about the addition of chemicals, it's about understanding the characteristics of your wastewater. pH, temperature, composition, where is it coming from and where is it going—all of these matters matter. Understanding how this work is important.” – Dr. Swati Sharma Whether you're hearing this episode for the first time or revisiting it, Dr. Sharma's research will leave you better equipped to tackle your next wastewater challenge with new insights and practical takeaways. Timestamps 01:00 - Trace Blackmore reminds you that next week there will be a new episode heard every day as we celebrate all 5 days of Industrial Water Week 06:00 - Introducing our top five episodes since Industrial Water Week 2023 08:03 - Interview with Doctor Swati Sharma of Water Engineering Incorporated, about 43:30 - Drop by Drop with James McDonald Connect with Swati Sharma, Ph.D. Phone: 402.521.4161 Email: ssharma@h2oeng.com Website:  www.h2oeng.com LinkedIn: in/swati-sharma-ph-d-91449518 company/water-engineering-inc Read the Press Release HERE Links Mentioned “How to Estimate the Best Treatment Conditions for Sunflower Oil Wastewater Using Advanced Electrooxidation Process” - Thesis by Dr. Swati Sharma Follow Dr. Swati Sharma on Google Scholar and be updated on her publications The Rising Tide Mastermind Top 5 Episodes since 2023's Industrial Water Week 341 Guarding Against Legionella: The Hidden Dangers of Dead Legs in Water Systems with lab partner Richard Philip Beckett 348 Credentials and Codes: Plumbing Strategies Against Legionella with Christoph Lohr 328 Industrial Water Week 2023: Pretreatment Monday with Wes Bryne 324 Endless Career Possibilities in Industrial Water Treatment with Chelsea Farmer Books Mentioned Wastewater Engineering: Treatment and Resource Recovery by Inc. Metcalf & Eddy Drop By Drop with James  In today's episode, we're thinking about annual reviews. Yes, annual reviews. They come due before you know it each year. Do you do annual reviews for your customers? If your answer is no, why not? I've always found annual reviews to be a great time to remind your customer of the value you bring to their operation. Industrial water treatment is important! Without it, it would cost more for them to operate. In many instances, their operations could be shut down. Plus, there are many safety aspects that good industrial water treatment brings to the table from helping keep boilers from exploding to helping minimize Legionnaires Disease. It's also a good time to get everyone on the same page to both maintain and improve the water treatment operations. Sure, it could be an opportunity for the end user to complain, but that's good! Would you rather they have an opportunity to tell you their issues face to face or in an email informing you they're changing industrial water treatment vendors? Be sure to document the annual review with a prepared document or presentation. Also be sure to follow up on any issues they have and commitments you have made.  Events for Water Professionals Check out our Scaling UP! H2O Events Calendar where we've listed every event Water Treaters should be aware of by clicking HERE. 

Everything changes today. Remember that. Wherever we end up, however this universe ends, it all starts today. Content warnings for this episode include: anger // discussion of deep water // taunting // aggression // substance use // knives as weaponsGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

How Veolia Prioritizes Health and Safety Worldwide? At Veolia, safety isn't just a requirement—it's embedded in the company's core values. Leading the charge is Arnaud Valleteau de Moulliac, Chief Executive Officer of Veolia Water Technologies. In this week's episode, Arnaud speaks with Scaling UP! H2O host Trace Blackmore about how safety initiatives are reshaping Veolia's culture around the world. Arnaud emphasizes that health and safety are non-negotiable: "It's a 24/7 commitment." This episode takes you inside Veolia's global approach, showing how the company's 8,000+ employees have integrated safety into their daily routines. What Drives Veolia's Health and Safety Initiatives? For Arnaud, safety comes from a personal place: “As a father of four, ensuring everyone gets home safely is paramount.” This family-first approach reflects Veolia's deep commitment to safety, which has been an ongoing focus for over a decade. “Ten years ago, we launched International Health and Safety Week, where every subsidiary worldwide participates in focused discussions and actions on safety.” This annual event creates a space for employees to assess their work environments, recognize potential risks, and form long-lasting safety habits. But at Veolia, safety isn't just about one week—it's about creating a culture that endures year-round. Fostering a Culture of Safety Every Day While International Health and Safety Week serves as a focal point, Veolia's goal is to make safety a daily priority. “We need to ensure that health and safety are part of our everyday routines, not just something we think about once a year,” Arnaud notes. To keep safety top of mind, managers at Veolia conduct at least six field visits each year, evaluating safety practices and identifying areas for improvement. Employees are encouraged to report near-misses and incidents, creating a culture were speaking up about safety is valued. “It's about creating an environment where people feel safe to voice concerns without fear of judgment,” Arnaud says. “Building trust is essential.” A Cultural Shift: Breaking Old Safety Norms One of Veolia's biggest achievements over the last decade has been a shift in how employees view safety. Arnaud recalls a time when raising safety concerns was often seen as a sign of weakness. Today, those conversations are welcomed and encouraged. “There used to be this mentality of being a 'superman'—toughing it out in unsafe conditions. That's behind us now, but we always stay cautious. The human element means we can never stop paying attention to safety,” Arnaud warns. This shift has been a significant victory for Veolia, but the work isn't finished. The company remains vigilant, continually adapting its safety approach to address both evolving risks and human factors. Celebrating 10 Years of Health and Safety Transformation As Veolia marks the 10th anniversary of International Health and Safety Week, Arnaud reflects on the company's progress. One key success has been the reduction in workplace accidents and the increasing willingness of employees to report safety risks. “Ten years ago, speaking up about safety could be seen as a weakness,” Arnaud explains. “Today, it's a sign of strength and responsibility.” This cultural change has transformed how employees view safety—not as a policy, but as a core value that protects their colleagues and ensures everyone returns home safely. Starting a Safety Culture: Insights for Small Teams For small businesses, building a safety culture might seem overwhelming. However, as Arnaud explains, it's not about financial investment—it's about leadership and intention. “Safety starts at the top. Being an exemplary leader doesn't cost anything. It's about creating policies and following through. Take time to sit with your team and ask, ‘What are the risks?' It's an investment in people, not just resources. Any company, no matter its size, can do this,” Arnaud emphasizes. Manager Visits: Fresh Eyes on the Ground As part of Veolia's commitment to safety, manager site visits provide an opportunity for leadership to spot issues that might have become invisible to regular operators. These visits aren't just procedural—they're a chance to bring fresh perspectives into the conversation. “Even non-operational colleagues—those from HR or finance—ask valuable questions during these visits. Their common sense often uncovers risks that might otherwise go unnoticed. Safety is about asking the right questions, not about being an expert,” Arnaud explains. One Key Takeaway: Lead by Example If there's one message Arnaud wants listeners to take away, it's this: “Be exemplary. It starts with you.” Veolia's success in transforming its safety culture is a powerful reminder that leadership and continuous vigilance are the best tools for creating a safe working environment, no matter the size of the operation. Stay Informed and Stay Safe! As Veolia's journey shows, building a culture of health and safety requires effort, commitment, and teamwork. Whether you are part of a large organization or a small team, Arnaud Valleteau de Moulliac's insights offer valuable lessons for promoting safety in any workplace. Timestamps 01:46 - Trace Blackmore thanks you for connecting at AWT last week and thanks you for the Innovation Award 07:54 - Upcoming Events for Water Treatment Professionals 11:13 - Interview with Arnaud Valeteau de Moulliac about his commitment to safety 40:05 - Drop by Drop with James McDonald  Connect with Arnaud Valleteau de Moulliac Email: arnaud.valleteau@veolia.com Website: www.veoliawatertechnologies.com LinkedIn: linkedin.com/in/arnaud-valleteau-de-moulliac-9b85353a/ www.linkedin.com/company/veolia-water-technologies/ Twitter: https://twitter.com/VeoliaWaterTech Read or Download Arnaud Valleteau de Moulliac's Press Release HERE Links Mentioned Ep 358 Safety First: Practical Tips, Big Results in Water Treatment Walk me through this “Safety Third” thing – Mike Rowe The Rising Tide Mastermind Scaling UP! H2O Academy video courses AWT (Association of Water Technologies) Drop By Drop with James  In today's episode, I have a “what if” for you. What if the temperature of the softener regeneration water drops in the wintertime? Now, if you're in an area with a warmer climate year-round, you may not have to worry about this, but for those who live in colder climates, it is something to consider. How could colder water temperatures cause an issue with softener regeneration? Have you ever considered this before? The answer is that water is denser at cooler temperatures. This could be especially important during the backwash step of the softener regeneration. A proper backwash is necessary to ensure efficient softener operation. It loosens the bed, minimizes pressure drop, cleans and classifies the resin, and maintains an even water flow across the cross-sectional area of the resin bed. Backwash flow rates must be high enough to expand the bed by 50% and typically last around 10 minutes or more. If the water is denser because it is colder, the same flow rate used in the warmer months can result in expanding the resin bed even MORE, which could ultimately lead to washing good resin down the drain. Resin manufacturers often have tables that show the required flow rate based upon water temperature. A big picture look at these tables roughly shows that, in Fahrenheit, when the temperature drops to half what it was in the summer months, the required flow rate could drop to half as well. Be sure to always refer to the resin manufacturer's specifications for actual design numbers, though.  2024 Events for Water Professionals Check out our Scaling UP! H2O Events Calendar where we've listed every event Water Treaters should be aware of by clicking HERE.   

With Thielia's divinity now out of her hands, she leaves the Cradle behind to find what has been lost…Content warnings for this episode include: death // parent-child conflict // romance // griefGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Thielia, Maiden of the Deep Woods, is Anjali Bhimani. The voice of Davos Halassian is Christian Carlson. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Ever continues her trip south, and finds the heart of her beloved forest, before arriving to a fated and foretold destiny on the steps of Temple Lybica…Content warnings for this episode include: The woods // grief // religious overtones // death // visions // fantasy violence // war // death of a loved one // funerals //Godkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Thielia, Maiden of the Deep Woods, is Anjali Bhimani. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Character and location leitmotifs by Si Rutherford of Sounds of Adventure. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

In today's episode I cover the latest stories from PetaPixel worth talking about this week. You can find the show notes here. https://liamphotographypodcast.com/episodes/episode-418-outdoor-line-pyxis-6k-luminar-neo-more

Welcome back to the Cradle, heretics. In our first episode, we meet Rake, a young man with a job to do, as he is set on a course of duty and vengeance by his dark patron…Content warnings for this episode include: Betrayal // substance use // fantasy violence // body horror // falling // unsafe water // power dynamics and struggle // religious overtones // complicated relationships // threats // gaslighting // parent-child conflict // death of a parent // sacrifice // confinement // murder // being followed // grief // knives as weaponsGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Avisan Eutoches is Tim Carlson. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

¿Qué tienen que hacer los países ante la avalancha de aplicaciones de inteligencia artificial? ¿Cómo se hace para aprovechar todo el potencial que tiene esta tecnología para mejorar la economía o la educación? ¿Cómo se evita, o minimiza, los usos indebidos de la inteligencia artificial? Varios países vienen aprobando sus propias estrategias nacionales en Inteligencia Artificial. El ejemplo más reciente está bien cerca. Hace unos días Brasil lanzó el Plan Brasileño de Inteligencia Artificial. Bajo el slogan “IA para el bien de todos”, el plan prevé una inversión de 4 mil millones de dólares en cuatro años para fomentar la incorporación de esta tecnología en el gobierno, en el sector industrial, en los servicios públicos, en la educación, entre otros. Otros países de similar tamaño a Uruguay con los que solemos compararnos también avanzaron en la materia. Por ejemplo, Nueva Zelanda, Irlanda o Portugal ya cuentan con estrategias de IA hace años. Uruguay tiene desde 2019, una Hoja de Ruta en Ciencia de Datos y Aprendizaje automático pero todavía falta una estrategia específica en Inteligencia Artificial. En la Rendición de Cuentas del año pasado, el gobierno encargó esta tarea a la Agencia Nacional de Gobierno Electrónico y Sociedad de la Información y el Conocimiento (Agesic). ¿Qué puntos debe incluir esta estrategia? ¿Cuál es el rol del estado, la academia y el sector privado en este plan?  Conversamos En Perspectiva con Virginia Pardo, ingeniera en Computación y directora de Sociedad de la Información en Agesic; Federico Lecumberry, doctor en Ingeniería Eléctrica, profesor de Procesamiento de Señales y Machine Learning en la Facultad de Ingeniería de la Udelar, e investigador asociado en el Institut Pasteur Montevideo; Álvaro Pardo, ingeniero eléctrico y co fundador de Digital Sense; y Diego Sastre, ingeniero en computación y cofundador de Pyxis.

In a prologue to our season, we meet Ever Halassian, preparing to leave her home of Temisset on a fated and forlorn journey south towards Glass…Content warnings for this episode include: Romance // heartbreak // conflict between romantic partners  // death of a parent // withholding information // religious overtones // griefGodkiller: Balance is performed by Em Carlson, Gina Susanna & Jannes Wessels. The voice of Verek Firesong is Christian Navarro. This season's dramaturge is Tim Carlson. Special thanks to our campaign artist, Mischi, who you can find @Mischiart on twitter! Our main theme for this episode, Light & Dark, was composed by Sean McRoberts. Music and effects by Epidemic Sound. Cartography for this series by Chaim Holtjer of Chaim's Cartography. For more stories, come follow us everywhere at @blackwaterdnd, and make sure to check out our Main Campaign on Monday nights at 8pm PST at twitch.tv/blackwaterdnd. To play your own campaign of Godkiller and dive into your own divinity, go support Godkiller by purchasing the ashcan on itch.io today, with the print version published soon by Evil Hat Productions. This show is made possible by our sponsors who graciously support us playing pretend and having feelings about it. We are grateful to be sponsored by Heroforge, who offer fully customizable miniatures made with their online 3D character creator! Head on over and design your own Godkiller, and get them printed in a variety of materials, including colour printing options! With new content added each week, check out www.heroforge.com to start bringing your character to life! This show is also proudly sponsored by Moonbeam, a better and safer way to stream! Dive into Realms for vibrant community hubs where creators keep 100% of what they earn while protected by Pyxis, a revolutionary moderation tool that learns and adapts to your boundaries. So check them out and join Moonbeam today! Finally, we're thankful for our Patrons for joining us on our second journey through the Cradle. You too can come join us on Patreon, where you can check out behind the scenes info, our talkback show Chatwater, as well as exclusive Godkiller bonus content and so much more. Head on over to patreon.com/blackwaterdnd for all the info. See you next time, heretics, and to all the gods out there, be safe!

Each week, we bring you insights from industry experts to help you scale up your water treatment knowledge and operations. This week, we're thrilled to share strategies for effective customer and employee surveys based on a recent interview with  Brian Katarski, Vice President of Sales and Marketing at AquaPhoenix Scientific. Brian's extensive experience in sales and marketing makes him a valuable source of knowledge on how to gather and use feedback to drive improvement. How Important is Feedback? “Feedback plays a very important role in all relationships: employees, coworkers, even your spouse.” - Brian Katarski Feedback is a cornerstone of growth. It empowers teams to improve by increasing their knowledge and confidence. Brian emphasizes the necessity of not just collecting feedback but using it as a foundation for continuous improvement. What is Feedback? “The most important part of feedback is that we have to use it as a basis for improvement. You cannot collect feedback just to ignore it, or justify it away, or pretend like it doesn't exist.” - Brian Katarski According to Brian, feedback should be actionable. Whether it's from customers or employees, feedback needs to be addressed constructively. Ignoring or dismissing feedback is counterproductive. Instead, look each other in the eye and commit to acting on the feedback received. How Do You Build a Healthy Culture of Feedback in Your Company? “The biggest piece to it is if you want to encourage this long-term over time is you have to respond to the feedback. You can't just ignore it, right? You can't ghost it, or you can't just think it didn't happen. or say. you know. justify it away. You have to respond to it in a way that lets somebody know ‘I heard you. I understand. Here's what we're gonna do with that information now', right. And that way they and they now know that we care. That we want to hear what they have to say whether it's an employee or a customer. They know that we're going to listen to what they have to say, and they'll be more willing to share that information with us.” - Brian Katarski Creating a healthy feedback culture starts with demonstrating that feedback is valued and acted upon. Brian highlights the importance of responding to feedback promptly and constructively. When employees or customers see that their input leads to real action, they are more likely to continue providing valuable insights. “You've got to try some different tactics and different things to try to reach certain people. Sometimes it's a quick paper survey. You know, maybe as you're walking out. Maybe you send an email or a link with your service reports whenever you send those off on Fridays or whenever you do it. Just different ways to do it, maybe put it on an invoice you're sending off, maybe have your marketing team sending those out, but you'll kind of figure out the best ways to gather that information depending on how people do it.” - Brian Katarski Diverse methods of collecting feedback ensure that you reach a broad audience and gather a variety of perspectives. Whether it's through paper surveys, emails, links in service reports, or even feedback sections on invoices, finding the right approach for your audience is key to building a robust feedback culture. How Do You Start and Encourage a Feedback Process? “Build out a plan around what you want to gather feedback on. Start with the end in mind.” - Brian Katarski Brian advises beginning with a clear plan. Identify what specific feedback you need and how you will use it to drive improvement. By focusing on the end goal, you can design a process that ensures the feedback is both meaningful and actionable. “It depends on what you want to gather and from who. It's gotta be simple and quick.” - Brian Katarski To encourage feedback, keep surveys short and straightforward, aiming for 1-5 questions. Use a variety of methods depending on your audience—quick paper surveys, emails, or links in service reports. Formal methods and scheduled discussions can be employed when necessary. Track and trend feedback over time to pinpoint areas of improvement. “At AquaPhoenix, we celebrate feedback because it gives us a chance to learn and improve.” - Brian Katarski A culture that values feedback fosters continuous learning and improvement. By celebrating feedback, you reinforce its importance and encourage ongoing participation from both employees and customers. What Are Some Common Feedback Mistakes to Avoid? “Humility is key. Accept feedback and resist the urge to get defensive.” - Brian Katarski Brian stresses the importance of humility in accepting feedback. Early in his career, he struggled with defensiveness, but now he focuses on understanding the underlying issues and using feedback to drive improvement. "Every time I feel that weird reaction, that sort of tension, I ask myself: What's driving that? Where's that coming from? And 9 times out of 10, it's my ego. It's me trying to protect myself because I don't want to admit that we were wrong, I don't want to admit that something happened, I don't want to accept that feedback. I think that's the biggest thing I can tell you." - Brian Katarski By recognizing the role of ego and defensiveness, Brian has learned to embrace feedback as a tool for growth. This shift in mindset allows him to find valuable insights in feedback, even when it's difficult to hear, and to continuously improve processes and relationships. We hope these insights from Brian Katarski help you implement effective feedback strategies in your organization. Stay tuned for next week's episode of Scaling UP! H2O, where we continue to bring you valuable industry insights. Timestamps 01:00 - Trace Blackmore asks you to look for the things that give you butterflies in your tummy because you are doing something new and challenging 04:05 - Upcoming Events for Water Treatment Professionals 09:45 - Interview with Brian Katarski, Vice President of Sales and Marketing at AquaPhoenix Scientific 51:00 - Drop by Drop with James McDonald  Connect with Brian Katarski Phone: 717.465.7859 Email: bkatarski@aquaphoenixsci.com Website: www.aquaphoenixsci.com LinkedIn: linkedin.com/in/bkatarski/ linkedin.com/company/aquaphoenix-scientific/ Read or Download Brian Katarski's Press Release HERE Links Mentioned Episode 325 Episode 298 Free Legionella Resources Page Industrial Water Week Resources Page Marriage App, Paired Hooper's Crab House, Ocean City, Maryland Hubspot CRM The Rising Tide Mastermind Scaling UP! H2O Academy video courses Submit a Show Idea AWT (Association of Water Technologies) Drop By Drop with James In today's episode, we're thinking about BOD and COD. First, what do these acronyms stand for: BOD and COD? How are they measured? Is one of them always equal to or higher than the other? Why would BOD or COD be used in water treatment? What can impact the BOD or COD of a water? What water treatment can change it? 2024 Events for Water Professionals Check out our Scaling UP! H2O Events Calendar where we've listed every event Water Treaters should be aware of by clicking HERE.  

Oggi parliamo di leadership e di come costruire e mantenere un team forte e coeso, un tema di fondamentale importanza per tutti gli imprenditori in ascolto. Dalle centinaia di interviste che abbiamo condotto, sappiamo che un team solido è una delle chiavi del successo di una startup. Al contrario, un team mediocre può decretare il fallimento di una startup. Per questo abbiamo deciso di invitare Tiziana Pregliasco esperta di questi temi, Tiziana è una consulente specializzata nella gestione e sviluppo delle risorse umane, nonché una sostenitrice del benessere organizzativo. Con oltre vent'anni di esperienza nel settore, ha lavorato in varie aziende multinazionali e di medie dimensioni. È laureata in Scienze della Formazione e ha conseguito diversi master e certificazioni, tra cui un master in Corporate & Business Coaching e un master a Yale su psycologial wellbeing.  Nel 2018, Tiziana ha fondato Pyxis, una società di consulenza che si focalizza sul benessere aziendale e sulla gestione delle performance. Pyxis offre servizi mirati a promuovere la cultura del benessere e una leadership positiva come strategie per attrarre, sviluppare e trattenere talenti nelle aziende. Inoltre, Tiziana ricopre il ruolo di mentor in Techstars e insegna temi legati al benessere, all'equilibrio tra vita lavorativa e privata, alla gestione dello stress e al coaching. NEWSLETTER Iscriviti a Il Digestivo: https://ildigestivo.substack.com/ SPONSOR Serenis è una piattaforma digitale per il benessere mentale. Seguendo il link: ⁠⁠www.serenis.it⁠⁠ troverai un questionario da riempire e da lì, tramite un algoritmo proprietario, la piattaforma ti connetterà con il terapeuta più adatto a te. Le sedute sono online e se il terapeuta selezionato non ti convince, puoi facilmente cambiare.  Serenis ha deciso di offrire un codice sconto per tutti gli ascoltatori di Made IT. Con il codice MADEIT7 avrai un colloquio gratuito e un'agevolazione di 7 euro sulle successive 3 sedute. SOCIAL MEDIA Se vi piace il podcast, il modo migliore per dircelo o per darci un feedback (e quello che ci aiuta di più a farlo diffondere) è semplicemente lasciare una recensione a 5 stelle o un commento su Spotify o l'app di Apple Podcast. Ci ha aiuta davvero tantissimo, quindi non esitate :) Se volete farci delle domande o seguirci, potete farlo qui: Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@madeit.podcast⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ LinkedIn ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@madeitpodcast⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠

Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers.    TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center.   You will find our full disclosures in the transcript of this episode.  Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma.  By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel.  So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact.  In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of events, such as disease progression, toxicity from treatment, if the patient was unable to go to surgery or had surgical complications, or if they had delay in starting the adjuvant therapy due to toxicity, and obviously, recurrence of melanoma or death from any cause. In that context, merely moving the 3 doses of pembrolizumab to the neoadjuvant setting saw an improvement in this two-year event free survival to 72% for the neoadjuvant therapy compared to 49% for the adjuvant therapy. That was quite an outstanding change. And again, noting the power of neoadjuvant treatment, really dictating the impact of anti PD-1, again, just with 3 doses moving from adjuvant into the neoadjuvant setting, and I think all of us were somewhat surprised to see that magnitude of a benefit. But it set up the current study very well, where we now look at combination therapy. Dr. Diwakar Davar: So let's move on to the phase 3 NADINA trial. Do you want to perhaps discuss the study design, particularly focusing on the EFS primary endpoint and maybe also touching on the different schedules? So, SWOG S1801 was a neoadjuvant study of 3 cycles of pembrolizumab and how did that compare and contrast to the neoadjuvant combination that was studied in NADINA? Dr. Jason Luke: Well, as you alluded to, NADINA investigated the regimen of nivolumab plus ipilimumab and compared that against adjuvant therapy with nivolumab alone. So, in the study, as you alluded, the dose and schedule of the two drugs used was nivolumab at 3 milligrams per kilogram, and ipilimumab with 1 milligram per kilogram. That was based on a series of signal finding and safety studies that had been previously done by the same group of authors identifying that as the optimal treatment regimen. And it's worth noting that's slightly different than the labeled indication that's generally used for those same drugs for metastatic melanoma, albeit that the NCCN also endorses this schedule. So, in the trial, 423 patients were randomized, 1:1 to receive either neoadjuvant therapy with those 2 doses of nivolumab plus ipilimumab as compared with standard adjuvant therapy with nivolumab following surgery.   Now, one interesting tweak was that there was an adaptive nature to the study, meaning that patients had a fiducial placed at the index lymph node, and after the neoadjuvant therapy in that arm, that lymph node was removed. And if the patient had a major pathological response, they did not go on to receive the adjuvant portion of the treatment. So it was adaptive because those patients who did very well to the neoadjuvant did not require the adjuvant portion. And in those patients who did not achieve a major pathological response, they could go on to have the adjuvant therapy. And that also included the BRAF therapy for those whose tumors were BRAF mutants.  It's also worth pointing out that the definition of event free survival was slightly different than in the S1801 study that was alluded to just a second ago. And here, EFS was defined from the date of randomization until progression due to melanoma or due to treatment. So that's slightly different than the definition in the S1801 trial. So, a somewhat complicated study, but I really applaud the authors because I think this study does mirror what we would likely be doing in actual clinical practice.  Dr. Diwakar Davar: So, just to briefly summarize the efficacy, and then to get your comments on this, the path response, the PCR rate was 47%. The major pathologic response rate, which is the proportion of patients with between 0% to 1/10% of residual viable tumors, was about 12%. And for a major pathologic response rate of 0% to 10% of 59%. And then the rest of the patients had either pathologic partial response, which was 10% to 50%, or pathologic non response or 50% or greater residual viable tumor, all assessed using central pathology grades. The one year RFS was 95% in the FDR patient population versus 76% in the pathologic partial response patient population, 57% in the pathologic non response patient population. So how do you view these results? Can you context the FDR rates and the EFS rates from NADINA relative to nivo-rela and also potentially SWOG 1801? Dr. Jason Luke: Well, I think these are very exciting results. I think that for those of us that have been following the field closely, they're actually not especially surprising because they mirror several studies that have come before them. When we put them in context with other studies, we see that these rates of major pathological response are consistent with what we've seen in phase 2 studies. They're relatively similar. Or I should say that the results from nivolumab and relatlimab, which was also pursued in a phase 2 study of somewhat similar design, are somewhat similar to this. So, combination immunotherapy does look to deliver a higher major pathological response than pembrolizumab alone, as was known in S1801. Which of course, the caveat being is these are cross control comparisons that we need to be careful about. So I think all of these are active regimens, and I think adding a second agent does appear to enhance the major pathologic response rates. When we look at the event free survival, we see something similar, which is that numerically it looks to be that combination immunotherapy delivers a higher event free survival rate. And that looks to be rather meaningful given the difference in the hazard ratios that were observed between these various studies. And here in the NADINA study, we see that 0.3 hazard ratio for EFS is just extremely impressive.  So the abstract then, from ourselves, out of these specific studies, what does this mean more broadly in the real world, where patients exist and the rest of the landscape for clinical trials? I think we can't take enough time to stop for a second and just think about what a revolution we've come forward in with immune checkpoint blockade and melanoma. When I started my career, now, more than 15 years ago, melanoma was the cancer that made cancer bad. And now here we say, in the highest risk of perioperative patients, we can deliver 2 doses of nivolumab and ipilimumab, and essentially half of the patients then don't need to go on, and more than half the patients don't need to go on to have a full surgery and don't need adjuvant therapy. And from what we could tell of a very, very low risk of every heavy recurrence of melanoma. Of course, there's the other half of patients where we still need to do better, but these are just fantastic results and I think highly meaningful for patients.   In the context of ongoing clinical trials, another abstract that was presented during the meeting was the update to the individualized neoantigen therapy, or V940 with pembrolizumab or against pembrolizumab alone. That's the KEYNOTE-942 study. In that study, they presented updated data at two and a half years for relapse free survival, noting a 75% rate without relapse. So those results are also highly intriguing. And these are in a similar population of very high risk patients. And so I think most of us believe that neoadjuvant therapy with this study in NADINA is now confirmed as the priority approach for patients who present with high-risk stage 3 disease. So that would be bulky disease picked up on a scan or palpable in a clinic. I think essentially all of us now believe patients should get preoperative immunotherapy. We can debate which approach to take, and it may vary by an individual patient's ability to tolerate toxicity, because, of course, multi agent immunotherapy does have increased toxicity relative to anti PD-1 alone. But we'll have to wait now for the full phase 3 results from the V940 individualized neoantigen therapy. And if those come forward, that will be an extremely attractive approach to think about for patients who did not achieve a major pathological response to neoadjuvant therapy, as well as of course to the other populations of patients with melanoma where we otherwise currently give adjuvant therapy stage 2B all the way through stage 4 resected. It's an amazing time to think about perioperative therapy in melanoma. Dr. Diwakar Davar: So this is clearly outstanding data, outstanding news. Congratulations to the investigators for really doing what is an investigative initiated trial conducted across multiple continents with a huge sample size. So this clearly appears to be, at this point in time at least, a de facto standard. But is this going to be FDA-approved, guideline-approved, or is it possible in your mind? Dr. Jason Luke: Well, that's an interesting question. This study was not designed with the intent to necessarily try to register this treatment regimen with the FDA. One would have to take a step back and say, with how powerful these data appear, it sort of seemed like it would be too bad if that doesn't happen. But all the same, I think the community and those of us who participate in guideline recommendations are fully supportive of this. So, I think we will see this move into compendium listings that support insurance approval, I think, very, very quickly. So, whether or not this actually becomes formally FDA approved or is in the guidelines, I think this should become the standard approach that is considered for patients, again presenting with high-risk stage 3 disease.  Dr. Diwakar Davar: Fantastic. So now we're going to go in and talk about a slightly different drug, but also from the melanoma context, and that is the safety and efficacy of RP1 with nivolumab in the context of patients with melanoma who are PD-1 failures. So, this is Abstract 9517. And in this abstract, our academic colleagues essentially talked about these data, and we'll start by describing what RP1 is. RP1 essentially is a HSV-1 based oncolytic immunotherapy. And RP1 expresses GM-CSF as well as a fusogenic protein, GALV-GP-R-. And in this abstract, Dr. Michael Wong from MD Anderson and colleagues are reporting the results of IGNYTE, which is a phase I trial of intratumoral RP1 co-administered with systemic nivolumab in patients with advanced metastatic treatment refractory cutaneous melanoma. And the data presented in this abstract represents data from a registration directed, abbreviated as RD, registration directed cohort of RP1 plus nivolumab in PD-1 refractory melanoma. So, let's start with the description of the cohort.  Dr. Jason Luke: Right. So, in this study, there were a total of 156 patients who were presented, and that included an initial safety and dose finding group of 16, as well as the RD cohort, as you noted, of 140 patients. And it's important to point out that this was a cohort that was selected for a very strict definition of progression on anti PD-1, or a combination immunotherapy as their immediately prior treatment. So, all of the patients in the cohort had exposure to anti PD-1, and 46% of them had anti PD-1 plus anti CTLA4, nivolumab and ipilimumab as their immediately prior therapy. This was also a group of relatively high-risk patients when one considers stage. So, within the stage 4 population, the entry here included 51% who had stage M1B, C, and D melanoma. And that is worth pointing out because this is an injectable therapy. So, trials like this in the past have tended to be biased towards earlier stage, unresectable or metastatic melanoma, meaning stage 3B, 3C, 3D and then stage 4m1a. Again, to emphasize the point here, these were pretreated patients who had a strict definition of anti PD-1 resistance, and over half of them, in fact, had high-risk visceral metastatic disease.  In that context, it's very interesting to observe that the overall response rate was described in the total population, as 31%, and that included 12% who achieved complete response. And so, again, to make sure it's clear, we're talking about a treatment where the oncolytic virus is injected into one or multiple sites of recurrent disease, and then the patients administer nivolumab as per standard. And so, I think these data are quite intriguing. Again, such a high- risk population and their maturity now, with a follow-up of over a year, I think, makes this look to be a very interesting treatment option.  Dr. Diwakar Davar: I guess on that topic of mature follow-up, it probably would be important for us to inform our audience that the top line data for the primary analysis was actually just released, I think, earlier today, and wherein the central confirmed objective response rate was 34% by modified RECIST and 33% by RECIST, clearly indicating that these responses, as you noted, very treatment refractory patient population, these responses were clearly very durable. So, you mentioned that there were responses seen in uninjected visceral lesions, responses seen in both PD-1 and PD-1 CTLA-4 refractory patients. Can you talk a little bit about the response rate in these high-risk subgroups, the uninjected visceral lesions, the patients who had both combination checkpoint and epidural refractory response rate by primary PD-1 resistance.  Dr. Jason Luke: Sure. You know, I think, again, to emphasize this point in the study, we saw that there were responses in the non-injected lesions, and I think it's really important to emphasize that. Some have referred to this as a putative abscopal like effect, similar to what is described in radiation. But it implies that local treatment with the oncolytic virus is triggering a systemic immune response. In the higher risk patient population, we'll note that whereas the overall response rate in PD-1 refractory patients was 34%, in the combination of PD-1 and CTLA-4 refractory patients, the response rate was 26%. So, [this is] still very good. And when we looked at that split by stage, as I alluded to before, in the population of patients that had, what you might call earlier unresectable diseases, so 3B through 4A, the response rate was 38%, and in the stage 4 M1b through M1d, it was 25%. So slightly lower, but still very good. And that would be as expected, because, of course, the patients with visceral metastatic disease have more advanced disease, but those response rates look quite good. Again, looking at the combination refractory population as well as the more high-risk disease. Dr. Diwakar Davar: So, clearly, these are very promising data and exciting times for multiple investigators in the field and the company, Replimune, as well. So, what are the next steps? I believe that a registration trial is planned, essentially, looking at this with the goal of trying to get this combination registered. Can you tell us a little bit about IGNYTE-3, the trial design, the control arm, and what you foresee this trial doing over the next couple of years?  Dr. Jason Luke: So, as this agent has been maturing, it's worth pointing out that the company that makes this molecule, called RP1, but I guess now we'll have to get used to this name vusolimogene oderparepvec as the actual scientific term, they have been having ongoing discussions with the FDA, and there is the potential that this agent could come forward on an accelerated path prior to the results being released from a phase 3 trial. That being said, the phase 3 confirmatory study, which is called the IGNYTE-3 study, is in the process of being launched now. And that's a study investigating this molecule in combination with nivolumab, as was alluded to earlier, and a randomized phase 3 design, where that combination is compared with a physician's choice, essentially a chemotherapy-based option.   In that study, it will be 400 patients with stage 3B through stage 4; patients will have progressed on anti PD-1, either as a combination or in sequence, and then come on the study to be randomized to either vusolimogene oderparepvec plus nivolumab versus that physician's choice. And the physician's choice includes chemotherapy agents, but also nivolumab plus relatlimab as another option, or an anti PD-1 monotherapy, if that's deemed to be a reasonable option by the treating investigator. And the primary endpoint of that study is overall survival. And unfortunately, in this highly refractory patient population, that's something that may not take long to identify with key secondary endpoints of progression free survival, as well as overall response rate. I'm quite enthusiastic about this study, given these data, which have now been centrally confirmed as you alluded to before. I think this is a very exciting area of investigation and really crossing my fingers that this may be perhaps the first locally administered therapy which does appear to have a systemic impact that can hold up in phase 3. Dr. Diwakar Davar: Very, very, very exciting results. And I guess it's worthwhile pointing out that this company also has got, I think, multiple studies planned with both RP1 and cutaneous squamous cell carcinoma in a solid organ transplant patient population where single agent activity has already been reported by Dr. Migden at prior meetings, as well as a novel trial of potentially RP2 metastatic uveal melanoma. So we'll now pivot to Abstract 6014. So, 6014 is a drug by a company known as Merus. Essentially, it's a very novel agent. Merus essentially is a company that is specialized in making bicyclics and tricyclics. And these are not bicycles or tricycles, but rather drugs that essentially are bispecific antibodies. And Merus essentially has come up with petosemtamab. I think we're going to have to figure out better names for all of these drugs at some point. But petosemtamab, or MCLA-158, essentially is a bicyclic, targeting both EGFR as well as LGR-5. So EGR-5, of course, is a known oncogenic driver in multiple tumor types, squamous, including non small cell lung cancer, cutaneous squamous cell carcinoma, but also head and neck squamous cell carcinoma. And LGR-5 essentially is leucine-rich repeat-containing G-protein coupled receptor 5, but it's a receptor in cancer stem cells and certainly highly expressed in head neck squam. And MCLA-158, or petosemtamab is a IgG one bispecific with ADCC-activity because of IgG1 backbone co-targeting EGFR and LGR5. Merus had earlier results that evaluated petosemtamab monotherapy. They defined the RP2D and second- and third-line head and neck blastoma patients with a respectable response rate of 37% investigator-assessed ORR with six months median DoR, and this was published by Ezra Cohen about a year or so ago.  In this abstract, Dr. Fayette and colleagues report on the results of the MCLA-158-CL01 trial, which is a trial of pembrolizumab plus petosemtamab in one front line head and neck squamous cell population. So maybe let's start with the description of the cohort. And it is a small trial, but we'll be able, I think, to dig into a little bit about why this might be exciting. Dr. Jason Luke: Yes. So, as alluded to, it's not the biggest trial as yet, but there were 26 patients with anti PD-1 treatment naive head and neck squamous cell carcinoma. And all the patients in the study did receive, as you alluded to, pembrolizumab plus petosemtamab. Based on the label for pembrolizumab, all the patients in this study were PDL-1 positive. So that's one point that it's worth pointing out to make sure that that's understood. This is the population of patients who would be expected to benefit from pembrolizumab in the first place. Now, in the abstract, they reported out only 10 response evaluable patients, but they updated that in the actual slides of presentation at the meeting. So among 24 patients that were alluded to, 67% were described as having had a response, although some of those were yet to be confirmed responses. And when it was evaluated by PDL-1 status, there didn't seem to be a clear enrichment of response in the PD-1 positive more than 20% group, as compared to the 1-19% group. That isn't especially surprising because that was a trend that one would see, presumably with pembrolizumab alone. But overall, I think these data are pretty exciting in terms of a preliminary study. Dr. Diwakar Davar: You know, you mentioned that the objective response rate was high, almost 60-something%. The prognosis of these patients is generally poor. The OS is typically thought of as between 6-15 months. And based on KEYNOTE-048, which was led by Dr. Burtness and colleagues, the standard of care in the setting is pembrolizumab +/- platinum based chemotherapy regimens. Allowing for the fact that we only have 10 patients here, how do you think these results stack up against KEYNOTE-048? And you made a very important point earlier, which was, by definition, pembro is on label only for the CPS. So PDL-1 score, at least in head and neck squamous cell carcinoma CPS and not TPS. But in the CPS 1% or greater patient population, where pembro is on label, how do these results stack up against the KEYNOTE-048 results. Dr. Jason Luke: Right. KEYNOTE-048 is considered the seminal study that dictates frontline treatment in head and neck cancer. And before we dive into this too far, we do want to acknowledge that here we're comparing 26 patients versus a phase 3 trial. So, we're not trying to get too far ahead of ourselves, but this is just a preliminary comparison. But in KEYNOTE-048, as you alluded to, two regimens were superior to chemotherapy. One was the pembrolizumab monotherapy, as well as pembrolizumab plus chemotherapy. So again, the study overall survival, of course, was much higher, the PDL-1 positive subgroup, which is what dictated the unlabeled use of this. But response to pembro monotherapy in that population of patients is still modest. We're talking about upwards of 20-30%. So, if you compare that to, again, preliminary evidence here from this trial of only 24 patients, that response rate of 60% seems extremely high. And so even if that were to come down somewhat in a larger data series of patients, that still looks to be quite promising as a treatment regimen, that might eventually even be chemotherapy sparing for this population of patients. I think this raises a lot of eyebrows that perhaps this dual targeting approach, EGFR and LDR-5, may bring something really important to the field that evolves it. Dr. Diwakar Davar: So, what are the next steps for petosemtamab? You mentioned that the activity was interesting. Are we going to see a larger trial? Any thoughts on where things are going to go?  Dr. Jason Luke: Well, based on the phase 2 data of petosemtamab alone, even without pembrolizumab, the molecule had already been given fast track designation by FDA, which means allowing for greater communication between the drug sponsor in the FDA and designing a seminal study design. One would assume that this trial will be rapidly expanded quite greatly, perhaps to 100 or 200 patients, to try to flush out what the real response rate is in a more meaningful number of patients. But I think these data will probably also trigger the design and probably near-term evaluation or expedited acceleration of a phase III clinical trial design that would potentially validate this against the current standard of care. So, I'm pretty excited. I think we'll see a lot more about this agent in the relatively near future. Dr. Diwakar Davar: So, finally, we'll pivot to the last abstract that we're going to talk about, which is Abstract 2504. It's a relatively interesting target, CCR8 monoclonal antibody. But this is the efficacy and safety of LM-108, and LM-108 is an anti CCR8 monoclonal antibody that is being developed by LaNova Medicine. And the results that are described, actually a pool set of results of combinations of LM-108 with anti PD-1, two separate anti PD-1, in patients with gastric cancer, mostly done ex-U.S., which is interesting because of this patient population, and it's a pool result of several, 3 phase 1 and 2 studies.  LM-108 is an Fc-optimized anti CCR8 monoclonal antibody that selectively depletes tumor infiltrating Tregs. The abstract reported a pooled analysis of three phase 1, 2 trials with 3 different NCT numbers that all evaluated the efficacy of LM-108 and anti PD-1 in patients with gastric cancer. So, let's start with the description of the cohort. Maybe, Jason, you can tell us a little bit about before you start, as you describe the cohort, sort of what we know, editorially speaking, about the difficulty with which Tregs depletion has been tried and obviously failed up until now in the tumor microenvironment. Dr. Jason Luke: Right. I think that's a really interesting comment. And so, for decades, in fact, targeting regulatory T-cell to alleviate immune exclusion in the tumor microenvironment has been of interest in immuno-oncology. And in preclinical mouse models, it seems quite clear that such an approach can deliver therapeutic efficacy. However, by contrast, in human clinical trials, various different Treg depleting strategies have been attempted, and there's really little to no evidence that depleting Tregs from human tumors actually can deliver therapeutic responses. And by that we're referring to CD-25 antibodies. The drug ipilimumab, the CTLA-4 antibody, was punitively described as a Tregs depleter preclinically, but that doesn't seem to be the case in patients. And so, in that background, this is quite an eye raiser that an anti CCR8 antibody could be driving this effect. Now, before we talk about the results of this trial, I will point out, however, that given the Fc-optimization, it's entirely possible that the Tregs are being depleted by this mechanism, but that more could also be going on. Because Fc gamma RII binding by this antibody that could be nonspecific also has the potential to trigger immune responses in the tumor microenvironment, probably mediated by myeloid cells. So I think more to come on this. If this turns out to be the first meaningful Tregs depletor that leads to therapeutic efficacy, that would be very interesting. But it's also possible this drug could have multiple mechanisms.  So, having said all of that, in the clinical trial, which was a pooled analysis, like you mentioned, of LM-108 in combination with anti PD-1 of a couple different flavors, there were 48 patients treated either with LM-108, with pembrolizumab, or with toripalimab, which is another anti PD-1 antibody. On the drug combination was, generally speaking, pretty well tolerated, noting grade 3 treatment related adverse events in the range of 38%, which is somewhat expected given combination immunotherapy. We talked about nivolumab and ipilimumab before, which, of course, gives even higher rates of immune-related adverse events, with the most common toxicities being anemia, lipase elevations, rash, ALC decrease; albeit, quite manageable. Dr. Diwakar Davar: So, what about the objective response rate? Can you contextualize the efficacy? And as you do that, maybe we'll think about what you'd expect in the context of, say, gastric cancer, especially in patients who've never really had a prior checkpoint inhibitor before. What do you think about the ORR? What do you think about the relative efficacy of this combination? Dr. Jason Luke: Well, so, in the study, they described overall response rate in the 36 patients as 36% and described immediate progression for survival of about 6.5 months. And so that was among patients who were treatment naive. And in second-line patients, they actually described an even higher response rate, although it was only 11 patients, but they're at 64%. And so, I think those data look to be somewhat interesting. When I was actually scrutinizing the actual data presented, it was of some interest to note that the quality of responses seemed to be about as good on the lower dose of LM-108, so 3 milligrams per kilogram as compared to 10 milligrams per kilogram. I think there's definitely more to learn here to try to optimize the dose and to fully understand what the overall efficacy of this treatment combination would be.  I would emphasize that in this disease, I think novel treatment strategies are certainly warranted. While anti PD-1 with chemotherapy has moved the needle in terms of standard of care treatment, it's really only a minor subset of patients who derive durable long-term benefit like we normally associate with immune checkpoint blockade. I think these are preliminary data. They're very intriguing.   You alluded to earlier that this population of patients was an Asian data set, and it is well known that the efficacy of chemotherapy and immunotherapy does appear to be somewhat enhanced in Asian populations, and that goes to distributions of metastasis and tumor microenvironment effects, etc. Very difficult to try to tease any of that out in this abstract, other than to look at these data and suggest that this is pretty interesting, both from a novel therapeutic approach, we talked about the Tregs consideration, but also straight up on the efficacy because I think if these data could hold up in a larger number of patients, and particularly in a western population of patients, I think it would be very intriguing. Dr. Diwakar Davar: Certainly, ASCO 2024 had a lot of interesting data, including data from targeted agents, the LAURA trial, ADCs. But just focusing on the immune therapy subset, we certainly saw a lot of great advances in patients who were treated with neoadjuvant as well as relapse refractory disease in the context of RP1 and then a couple of newer agents such as this petosemtamab as well as LM-108. And of course, we cannot forget to highlight the extended DMFS data from the pembro vaccine study from KEYNOTE-942.  Jason, as always, thank you for taking a little bit of time out of your extremely busy schedule to come and give us insights as to how these agents are impacting the landscape. We really value your input and so thank you very much.  Dr. Jason Luke: Thank you for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for your time today. You will find the links to all the abstracts that we discussed in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. So, thank you.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

The Lumix S9 is a rather unusual camera from Panasonic that we definitely have some thoughts on, so we go deep in this episode on its specs and details. Also, we compare the value of the Blackmagic Cinema Camera 6K and the Pyxis, and retrospect on a few recent video and photo shoots. Want to send us a question or comment, or just learn more about the show? Check out our website at https://cameragearpodcast.com, or email us directly at cameragearpodcast@gmail.com. Some links below to product sites are affiliate links and may result in a commission to the Camera Gear Podcast. Links: Blackmagic Cinema Camera 6K Blackmagic Pyxis 6K Panasonic Lumix S9 [Adorama]

Welcome to the latest episode of the V Podcast, where we bring you all the usual big tunes, fresh dubs, and forgotten classics, catering strictly for the underground. This month, we're dedicating the episode to the legendary MC Conrad, who recently passed away. MC Conrad was a huge influence and a beloved figure in the Drum and Bass community. Bryan was a big fan and pays tribute to him in this episode. Stay connected with us on social media and subscribe to the V Podcast on your favorite platform to stay updated on all the latest episodes. 1. Zero T - Jazz Type Thing 2. Makoto and L-Side - Nothing Like This 3. Frank Carter and L-Side - Do 4 Love 4. Illmatika and L-Side - Outside 5. Zoro - When the Lights Go Out 6. Phentix - Exit 7. Alibi - Cause and Effect VIP 8. L-Side - Past Lives 9. Paul T and Edward Oberon, Riya - Soul Connected 10. Melinki, Pyxis, T.R.A.C. and Collette Warren - Go Back 11. A-Audio - When I Was Young 12. Mampi Swift - Attack Me 13. Carlito - Learn to Fly 14. Motiv - Walkin Jazz 15. Adam F and MC Conrad - F Jam 16. MC Conrad - Promise Land 17. Makoto and MC Conrad - Merchant Blessing 18. MC Conrad - Lean Upwards 19. Paul SG, T.R.A.C. and MC Conrad - The Pursuit 20. MC Conrad - The Western 21. L-Side and MC Conrad - La Dolce Vita 22. MC Conrad and Total Science - Soul Patrol 23. Makoto and MC Conrad - Golden Girl 24. MC Conrad - Futures Calling 25. Carlito - Don't You Know 26. L-Side and MC Fats - Love in the Heart 27. Command Strange and L-Side - Angry Tune 28. Level 2 - Your Body 29. The Sauce and MC Fox - First Class 30. Sl8r, L-Side and MC Fox - Slammer 31. Shy FX - Gideon a Charge 32. Unglued and Alibi feat. Sweetie Irie - Dubbin Out 33. Alibi - Majesty 34. Break - Something 35. Break - All You Gotta Do 36. Simon Bassline Smith - Junglist Selectors 37. Melocular and L-Side - So Ruff 38. L-Side - Bionic Man (L-Side Remix) 39. Shy FX - Rudeboy Design 40. Think Tonk - Bury Dem (L-Side Remix) 41. Zero T - Ladies and Gentleman 42. Myriad - Ready to Play 43. Nazca Linez - Acid Fashion (Serum Remix)

01. Sless - Half Life 02. Fred V - Collide (feat. Dnmo & Paul Dowling) 03. Mage - Dont Make Me 04. Caitc - Fever 05. S9 - Head Above Water (Original Mix) 06. Doctor Werewolf - Close 2 Me 07. Pendulum - Girl In The Fire 08. Andromedik & Rani - Bleed The Same 09. Lynel & Brian Brainstorm - Can't Stop Raving feat. Drea Perlon 10. Dr. Apollo, General Levy - Remedy (Enta Remix) 11. Dj Fresh & Ericcongerai - The Martians 12. Streets Of Rage - Mind Clear 13. Trickyskill - Solar Collapse 14. Pendulum - Blood Sugar (Original Mix) 15. Jenske - Lucky Ones 16. Mayak (Df) - Project 7 17. Esym - Someday 18. Pythius, Reebz, Hysta - In My Head (Hysta Remix) 19. Screamarts - Coalesce (Audio Remix) 20. Current Value - Ofc 21. Skantia - Submergence 22. [Borders], Puzzle & Monist - The Tide 23. Petarda - Technology 24. Steplexx - Again 25. Streets Of Rage - Reminder 26. Pop Off - I Fell But You Don't Mind 27. Nick Reach Up, Dave Spoon, Final Cut - Dance The Night Away (Syran Remix) 28. Neibex - Enriched Water 29. Adam F - Brand New Funk Revisited (Bladerunner Remix) 30. Skantia - Zidane Dub 31. T95 - Dirty South 32. Secret Tape, Rohaan - D.L.T.S. 33. In:Most & Mistrust - Close 34. Mooncat - Deep Blues 35. Order Up - Funk Train 36. Leemo - Do You 37. Benny Page, Sweetie Irie - Fallen Soldier (Lowriderz & Distant Future Remix) 38. Street Creeps - The Forecast Is Genocide 39. Objectiv - Seasoned 40. K Motionz & Arrdee feat. Riko Dan - Heavyweight 41. Enta - If You Leak This You'Re A Prick 42. Heskk - Juice From Fruit 43. Maurizzle, Temple - Pop It 44. Es, Stillz - Aura 45. Primate - Abundance 46. Silvz - Mike Tyson 47. Kazuya - Techno Nightmare 48. Mylk - Tera 49. Subsonic - Do Your Thang (Mozey Remix) 50. Bassdubbers - Put Em Down 51. Manifest & Tanc - Stingray 52. Kritikal - T.M.B. 53. Chef Boyarbeatz - Ready 54. Dj Brockie & Ed Solo - System Check (Dj Limited Remix) 55. Conrad Subs - Smash N Grab 56. Dj Rusty - Thunderbolt 57. Speaker Louis - Soundclash 58. Champagne Breakfast - Gucci Sliders (Teej Remix) 59. Killswitch - Gotti 60. So-Low - Outcry 61. Dawn Raid - Days Are Numbered 62. Killjoy - More Lighter 63. Krugah - Inna Babylon 64. Kuttin Edge - Laguna Seca 65. Hugh Hardie - Yuzu 66. Msdos - Parasol (Dash Remix) 67. Kuttin Edge - Waiting (All Night) 68. Neuronex - Ivory 69. Banditt & Kippo - Uber 70. Viewer - Thoughts 71. Monty, Trail - In The Cut 72. Dephzac & Simon V - Aurora 73. Shaun Gazkinz - New Day (Original Mix) 74. Pyxis, Finnadrift, Kinsella - Unto You 75. Fred Again.. & Anderson .Paak & Chika - Places To Be

Dr. Diwakar Davar and Dr. Jason Luke discuss key abstracts from the 2024 ASCO Annual Meeting that explore triplet therapy in advanced melanoma, TIL cell therapy in immune checkpoint inhibitor–naive patients, and other novel approaches that could shape the future of immunotherapy in melanoma and beyond.  TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I'm delighted to have my friend and colleague, Dr. Jason Luke, on the podcast today to discuss key abstracts in melanoma and immunotherapy that will be featured and highlighted at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapeutic Center, as well as the associate director for clinical research at the University of Pittsburgh's Hillman Cancer Center.  You will find our full disclosures in the transcript of this episode.  Jason, as always, it's a pleasure to have you on this podcast to hear your key insights on trials in the immunotherapy space and melanoma development paradigm, and to have you back on this podcast to highlight some of this work.  Dr. Jason Luke: Thanks so much for the opportunity to participate. I always enjoy this heading into ASCO.  Dr. Diwakar Davar: We're going to go ahead and talk about three abstracts in the melanoma space, and we will be starting with Abstract 9504. Abstract 9504 essentially is the RELATIVITY-048 study. It describes the efficacy and safety of the triplet nivolumab, relatlimab, and ipilimumab regimen in advanced PD-1 naive melanoma. So in this abstract highlighted by Dr. Ascierto and colleagues, they report on the results of this phase 2 trial in this setting. By way of background, PD-1 inhibitors and immune checkpoint inhibitors starting in PD-1 and CTLA-4, as well as PD-1 and LAG-3, are all FDA-approved on the basis of several pivotal phase 3 trials, including KEYNOTE-006, CheckMate-066, CheckMate-067, and most recently, RELATIVITY-047. Jason, can you briefly summarize for this audience what we know about each of these drugs, at least the two combinations that we have at this time?  Dr. Jason Luke: For sure. And of course, these anti PD-1 agents, became a backbone in oncology and in melanoma dating back to more than 10 years ago now, that response rates in the treatment-naive setting to anti PD-1 with either pembrolizumab or nivolumab are roughly in the range of mid-30s to high-40s. And we've seen clinical trials adding on second agents. You alluded to them with the seminal study being CheckMate-067, where we combined a PD-1 antibody and CTLA-4 antibody or nivo + ipi. And there the response rate was increased to approximately 56%. And more recently, we have data combining PD-1 inhibitors with anti-LAG-3. So that's nivolumab and relatlimab. Now, in that trial, RELATIVITY-047, the overall response rate was described as 43%. And so that sounds, on a first pass, like a lower number, of course, than what we heard for nivolumab and ipilimumab. We have to be cautious, however, that the cross-trial comparison between those studies is somewhat fraught due to different patient populations and different study design. So I think most of us think that the response rate or the long-term outcomes between PD-1, CTLA-4, and PD-1 LAG-3 are probably roughly similar, albeit that, of course, we have much better or much longer follow up for the nivo + ipi combo.  The one other caveat to this, of course then, is that the side effect profile of these two combinations is distinct, where the incidence of high-grade immune-related adverse events is going to be roughly half with nivolumab and relatlimab, a combination of what you would see with the nivolumab and ipilimumab. So that has caused a lot of us to try to think about where we would use these different combinations. But we do see that all of these treatments can land a durable long-term response in the subset of patients that do have an initial treatment benefit. The landmark, I think, for the field has been the 7-and-a-half-year median overall survival that we've seen with PD-1 plus CTLA-4, nivo + ipi; of course, we don't have such long-term follow up for PD-1 and LAG-3. But I think that's the setting for thinking about the rationale for combining a triplet regimen of PD-1, CTLA-4, and LAG-3. Dr. Diwakar Davar: So, Jason, in your mind, given the difference in the disparity and durability of the responses for the 067 regimen of nivo-ipi, and the RELATIVITY-047 regiment of nivo-rela, what is the standard of care in the U.S., and how does it change in the rest of the world, knowing that nivo-rela is not necessarily approved in all jurisdictions? Dr. Jason Luke: So this is a major complication in our field, is that there is perhaps not complete agreement across the world in terms of what the frontline standard of care should be. I think most United States investigators, or those of us that really treat melanoma most of the time, would suggest that a combination regimen, given the enhanced response rate and longer-term outcomes, should be the consideration for the majority of patients. In fact, in my practice, it's hard to think of who I would treat with a monotherapy PD-1 approach in the PD-1 naive setting. So either nivo + ipi or nivo + rela. As you alluded to however, in other regulatory settings throughout the world, combinations might not actually even be approved at this point. So PD-1 monotherapy would be the backbone of that setting. It does set up some complications when you think about a comparator arm; say you were going to look at various combinations, probably PD-1 monotherapy would be the worldwide comparator. You have to understand though, in the United States, I think that that's a less attractive option. Dr. Diwakar Davar: So in RELATIVITY-047, Dr. Ascierto and his colleagues are looking at generating a triplet. And in this case, they looked at this in the context of frontline metastatic melanoma, 46 patients. Very interestingly, the dose of ipilimumab studied here was 1 mg/kg through 8 weeks, not the 3 mg/kg every three weeks times four doses using 067, or even the low dose ipilimumab regimen that you studied in the second line setting, which was 1 mg/kg every 3 weeks for 4 doses. So let's talk about the results and specifically the implications of potentially studying lower doses of ipi. Dr. Jason Luke: I appreciate you raising that point. I think it's really important as we think about this dataset because this triplet regimen is not by any means the only version of a triplet that could be developed using these agents. So just to give the high-level numbers from the abstract, we see from these data that the overall response rate is described as 59% and 78%, a disease control rate with patients having an unreached link. So duration of response of unreached, and then the progression-free survival at about 5 months. So those are really interesting data. But as was alluded to, it's not totally clear to me that that's the best that we could do with this regimen.   Now, you alluded to this low-dose ipilimumab schedule at 1 mg/kg every 8 weeks, and it's really important to note that we have no benchmark for that regimen in melanoma oncology. And in fact, the one study that used that regimen, which was the adjuvant study of nivolumab and ipilimumab, known as CheckMate915, is in fact the only immune checkpoint inhibitor study in melanoma oncology that was actually negative. That study noted no benefit to adding ipilimumab at 1 mg/kg every 8 weeks on top of nivolumab, again, the adjuvant setting. So it's a little bit curious to then understand what it means in this study to have that amount of ipilimumab added to the rela-nivo backbone. And that manifests in a few different ways. We see the response rate here at 59%. Again, if you compare that just against the standard nivo + ipi dosing schedule, it's about the same. So is that really an advantage to having the triplet as compared to just doing standard nivo + ipi?   We do see that it manifests in a slightly lower rate of grade 3/4 immune-related adverse events, at 39%. That's a little bit lower than what we'd expect for standard nivo + ipi. But again, I think that that emphasizes to me the possibility that some efficacy was left on the table by using this very low dose ipilimumab regimen. I think that's really a concern. It's not clear to me that these triplet data really differentiate from what we'd expect with the already approved regimen of nivo + ipi. Therefore, it makes it difficult to think about how would we really want to move this regimen forward, or should there be more work done about dose and schedule to optimize how we might want to do this?  Dr. Diwakar Davar: As far as triplet therapy in the context of frontline metastatic melanoma, meaning triplet immune therapy, because there are at least several targeted therapy triplets that are FDA-approved, [but] not necessarily widely utilized. How would you summarize the future for triplet therapy? Do you think it's potentially attractive? Do you think it's very attractive with some caveats? Dr. Jason Luke: Well, I think it's attractive, and we have 3 independently active agents. And so I do think it's a priority for the field to try to figure out how we could optimize the therapy. We've had such a revolution in melanoma oncology, talking about 7.5-year median survival from CheckMate-067, but that still implies that 7.5 years, half the patients have passed away. There's more to do here. And so I do think it should be a priority to sort this out. I guess I would be cautious, though, about advancing this regimen directly to a phase 3 trial because it doesn't seem clear to me that this is optimized in terms of what the outcome could be. If we're willing to tolerate higher rates of toxicity from other dose schedules of nivo-ipi alone, then I think we should do a little bit more here to potentially explore the space that might be possible to increase that overall response rate a little more without getting into a completely exaggerated toxicity profile that would be unacceptable. So, I do think it's exciting, but there's possibly more to do before really think about going big time with this. Dr. Diwakar Davar: Great. So now we'll switch gears and move from frontline metastatic melanoma to the second line and beyond looking at a new agent and contextualizing the effects of that actually in the frontline settings. So Abstract 9505 describes the efficacy and safety of lifileucel, which is essentially autologous tumor-infiltrating lymphocyte cell therapies, also known as TIL, in combination with pembrolizumab in patients with ICI naive, so not necessarily pretreated, but ICI naive metastatic or unresectable melanoma. This is data from the IOV-COM-202 Cohort 1A oral abstract presented by Dr. Thomas and colleagues. In this abstract, Dr. Thomas and colleagues are presenting data from the 1A cohort, which is the phase 2 portion of the frontline trial that is evaluating autologous TIL with pembro in checkpoint inhibited naive metastatic melanoma.  By way of background, TIL is FDA approved on the basis of several cohorts from a phase 2 trial. The data has been presented multiple times now by Drs. Sarli, Chesney, and multiple colleagues of ours. And essentially autologous TIL, which is generated from a surgical procedure in which a patient undergoes a surgery to extract a tumor from which T cells are then grown after ex vivo expansion and rapid expansion protocol. The entire procedure was essentially pioneered by several colleagues at the NCI, primarily Dr. Steve Rosenberg, and this approach produces objective response rates of approximately 31% to 36%. And the most recent publication demonstrated that at median follow up of approximately 2 years, the median duration of response was not reached. The median OS was about 14 months and PFS was about 4 months or so. So, can you contextualize the results of the abstract in the frontline setting? And then we'll talk a little bit about where we think this is going to go. Dr. Jason Luke: So I think this is a timely study given the recent approval. And in the abstract presented here, we see an early data cut from the PD-1 naive study, as you alluded to. So here we had 22 patients and distributed across various states of advanced melanoma. Ten out of the 22 had M1C, but there also were smatterings of earlier M1A and M1B at 18.2% and 9.1%. So this is important, as we think who the treatment population is that's going to be optimized with a TIL procedure. The median sum of diameters, meaning how much tumor burden the patients have, was about 5.5cm, and I'll note that that's a relatively modest amount of tumor burden, albeit not that unusual for an early-stage trial. So of the patients that participated, 8 had BRAF mutations so that's 36%. That's not that high, but it's reasonable. And I think the important overlying number, the response rate so far in the study, with about 17 months of follow up, was 63.6%, and that includes 22% or 23% having complete response. So those are interesting data.  And another point that was made in the abstract, which we've all seen, is that responses to TIL, all of immunotherapy but especially TIL, do seem to mature over time, meaning they deepen over time. So it's possible the response rate could go up some extent as we watch this study advance. So I think these are exciting data on some level. Also, a 63.6% response rate sounds pretty impressive, but we do have to put that in the context of a double checkpoint blockade, which we just got done discussing, gives you almost a 60% response rate, 59% response rate. So then the question really is: Is it worth the amount of effort that we could go into generating a TIL product in a treatment naive patient, and put them through the lymphodepletion that is associated with TIL and the high dose interleukin 2 treatment that accompanies the reinfusion of the TIL, if you're going to get a response rate that's roughly the same as what you would get if you gave them off the shelf nivo plus ipilimumab?  At this point it's a little bit hard to know the answer to that question. I think it could be possible that the answer is yes, because we don't know exactly which populations or patients are most likely to benefit from each of these therapies. And if it could be teased out who's not going to benefit to nivo + ipi from the get-go, then of course, we would want to offer them a therapy that has that frontline potential, durable, long-term response. But I have to say, on a one-to-one with TIL therapy, you get a lot of toxicity initially with the treatment; with nivo + ipi on the back end, you get a fair amount of toxicity with the treatment. How are we going to judge those two things? And I think we probably need a larger dataset to really have a good handle on that.  So these are interesting early data, but it's not totally clear to me that even if this holds up all the way through the trial, and we're going to talk about the design of the registration trial here in a second, a 60% response rate on its own without further biomarker stratification is a little bit hard for me to see in clinical practice why we would want to do that, given we can already just go off the shelf and give checkpoint inhibitors. Dr. Diwakar Davar: So that brings us to TILVANCE-301. So TILVANCE is a phase 3 trial. It's a registration intent trial by our Iovance colleagues evaluating the pembro-TIL regimen versus pembrolizumab alone. So in this phase 3 trial, approximately 670 patients will be randomized to either arm A, which is lifileucel + pembro. And in this arm A, patients are going to be getting lifileucel with the tumor resection, non-myeloablative lymphoid depletion, the lifileucel and abbreviated course of high-dose IL-2, and thereafter, continued pembro for the study mandated duration versus arm B, where patients will be getting just pembrolizumab monotherapy per label. Arm B patients, per the design, may cross over to receive TIL monotherapy at the time of central-blinded, radiology-confirmed disease progression.   The study design otherwise is fairly routine and, per most of our registration trials these days, patients have actually been permitted to receive neoadjuvant and adjuvant therapy, including checkpoint inhibitors, as long as the receipt of the therapy was more than 6 months prior to the inclusion of the patient in that registration trial. The dual primary efficacy endpoints as stated are BICR-assessed objective response rate as well as PFS, and the key secondary endpoint is overall survival.   So Jason, what are your thoughts on the study design and potentially the regulatory implications, particularly given, one, the control arm of pembro monotherapy, and two, the role of TIL crossover to receive TIL monotherapy at the time of BICR mandated progression for arm B? Dr. Jason Luke: So this goes to a few points that we've touched on already in the discussion here. When we think about the primary endpoints for this study, with one of them being overall response rate, one has to assume that that's a given that they would get that. I feel like that's a low bar. And we go back to that cross-trial comparison. If their results end up being that the response rates are about 60%, I don't know that that differentiates necessarily from what's already available in the field with combination immune checkpoint blockade. For the purposes of the study that would mean it's a positive study, so I think that would probably be good. But again, the comparator to pembrolizumab monotherapy, I think some of us would argue, isn't really consistent with what we would do with a patient in our clinic. So it's not that it's bad per se, but I think there's going to be a whole lot of cross-trial comparison. So if the study is positive, that would be good for getting the drug available. It's still a bit hard though, based on the preliminary data that I've seen, to imagine how this would have uptake in terms of utilization as a frontline therapy.  You alluded to the crossover, and I think there, the assumption is that patients who get TIL therapy as a second line perhaps would have an attenuated benefit. But I'm not sure that's really true. It certainly looks from the data that we have, like the patients who benefit most from TIL are going to be those who didn't respond to anti PD-1 in the front line. So I'm not sure how much difference there's going to be between first- and second-line TIL therapy, but those data will kind of wait to be seen. So I think it's an important study. Of course, the accelerated approval of TIL as a later line therapy is dependent on this trial being positive. So there is some risk that if this trial ended up not being positive, that that could have regulatory implications on the utility or availability of TILs, a subsequent line therapy. But all of these, I guess we'll have to wait to see the results. We do hope for a positive trial here, although I think it'll be nuanced to sort of interpret those data given that pembrolizumab monotherapy control arm.  Dr. Diwakar Davar: Fantastic. So we've learned a lot about TIL, both its use in the second-line setting and this very exciting but potentially risky frontline trial that is ongoing at some centers in the United States and certainly a lot of ex-U.S. enrollment.   So we'll now pivot to a related product which actually belongs to a much larger class of agents that are antigen specific T-cell therapies in a variety of different formats. And that is Abstract 9507, which is the “Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM).” Now, in this abstract, Dr. Omid Hamid and colleagues reported the results of this phase 1 trial. As a disclosure, I'm an investigator and the last author on this manuscript. Jason, it would be important for our audience, for us to maybe firstly, outline the PRAME as a target, and then the ImmTAC as a platform prior to discussing these results. So let's start with the target PRAME, which I think is a target that you know well. So why don't you start with the target and we'll talk a little bit about that and then the platform? Dr. Jason Luke: Yeah, so I think for the audience, being aware of PRAME, or the Preferentially Expressed Antigen in Melanoma, is going to be quite important moving into the future. So PRAME as a therapeutic target is a cancer testis antigen that's overexpressed in tumor tissues. And of course the name has melanoma in it, but it's not uniquely present in melanoma. So the expression patterns of PRAME as a target are very high in melanoma. So in cutaneous disease, this is upwards of almost 100%, somewhere between 95% and 100%, in metastatic melanoma tissues. And PRAME has several different roles on a molecular level, although I don't think for our purposes here, it's so much important to be aware of them, but rather that this is a very highly expressed target, which then can make it attractive for using T cell receptor-based therapies. And so in the case we're talking about here on the ImmTAC platform, that's a CD3 PRAME×CD3 bispecific approach. But of course there are other approaches that can also be taken, such as TCR T cells that directly go after PRAME itself. Dr. Diwakar Davar: Let's now talk about the platform and how it differs from some of the other antigen targeting platforms that you have just alluded to. I think the Immtac platform is basically a fusion protein comprising engineered TCRs with a CD3 specific short chain variable fragment. And then the engineered TCR therefore binds antigens in an HLA dependent fashion. But you know quite a lot about some of these alternative platforms, and I think it'll be important to contextualize for the audience the difference between ImmTAC, which is a prototype drug that is already approved in the context of tebentafusp. But how does this differ from some of the other more nuanced platforms, such as the Immatics TCR or TCR platform and TScan TCRT nanoplasmonic platform.  Dr. Jason Luke: Right. So the ImmTAC platform as alluded to is already approved on the market with tebentafusp, which is the gp100-CD3 bispecific molecule. And the advantage of that approach is infusion off the shelf of a drug. The downside of it is that it is a weekly dosing strategy as it stands now. And there are some complicated disease kinetics associated with treatment response, which we'll come back to in the context of the PRAME bispecific. Those are, in contrast with T-cell receptor-transduced T cells, as an alternative strategy, which is a form of adopted cell transfer. So we just got done talking about TIL therapy, which of course, is trying to take lymphocytes out of the tumor and grow them up and then give them back. Here with TCR-transduced T cells, we're talking about taking leukopak from the blood and then using different transfection approaches to try to insert into the lymphocytes of the patient a T cell receptor that recognizes to a certain cancer antigen, in this case, PRAME.  So you alluded to a couple of different companies that have different platforms to do this. Immatics has a molecule called IMA 203, for which there have been data disclosed in the past year, again showing some very interesting responses in patients who have highly refractory melanoma. That process, though, again, does require lymphodepletion before you reinfuse the cells. Again, in contrast, the ImmTAC, which is an off the shelf revenue administer, there you have to make the product and then bring the patient back, lymphodeplete, and give the cells back. Immatics platform uses a viral transfection vector. The T scan approach that you alluded to before uses an approach of a mixed system on multiple HLA backgrounds to try to get past HLA-A*02:01 only, and in this case, uses a plasmid-based transfection syndrome that perhaps can be more broadly utilized given the lack of a lentiviral vector.   So this is a complicated area of technology that starts to get into immune engineering, and I think for the purposes of this discussion, we don't want to belabor it. But both of these technologies, talking about the CD3 bispecific with the off the shelf aspect of it and the adoptive cell transfer, each of these using a T cell receptor-based therapy to try to go after PRAME, I think have very high upsides, and I think we'll initially see it in melanoma over the next year or so. But this is likely to be relevant to multiple tumor types beyond melanoma.  Dr. Diwakar Davar: So let's discuss the results of this phase 1 trial. IMC-F106C, like all other ImmTAC, is administered intravenously and does require step-up dosing. You alluded to the fact that the tebentafusp was approved, and it's one of those drugs that is fortunately otherwise administered weekly, which can be difficult for the patient and requires at least the patient spend the first 3 doses overnight under some kind of monitoring, whether it's in the hospital or extended outpatient monitoring, for at least 23 hours. The efficacy of this agent and this platform appears to be surprising in that you tend to see a relatively low RECIST response rate. We'll have you comment a little bit on why that is the case and what may be the role of ctDNA, as opposed to conventional RECIST in assessing response.   At least in this trial, they mandated pre-testing, but did not require it for study enrollment. And pre-positivity was defined using immunohistochemistry with a relatively low H-score of 1%. And the molecular response definition was a 0.5 log or a 68% ctDNA reduction just prior to the first imaging assessment. So how do you contextualize the results? But maybe before you talk a little bit about the results, the ctDNA aspect, that was a recent publication by Drs. Rich Carvajal, Alex Shoushtari, and I think you are also involved in that.  Dr. Jason Luke: So, I think an interesting observation around tebentafusp has been that ctDNA may be a better predictor of long-term outcomes. And how you define ctDNA response is still something that the field is grappling with, albeit that I think is going to be an important consideration as we think about these novel therapies, these ImmTACs and other CD3 engagers moving into the future. But for the purposes of the abstract here, we see that in the population of patients treated, there were 46 patients with cutaneous melanoma. The majority got monotherapy with IMC-F106C, and that's the PRAME bispecific. So 40 patients that got monotherapy and six who got a combination with checkpoint inhibitor. All these patients had prior treatment with immunotherapy, and most of them had PD-1 and CTLA-4 antibody with a small spanner that also had BRAF inhibitors.  In terms of that PRAME testing that you alluded to, based on the immunohistochemistry H-score greater than 1%, 35 out of 40 patients were positive, so they defined 5 as negative. And we could come back if we have time, but there are other ways to do PRAME testing as well that I think may become unique for different agents, maybe an important biomarker. In the data, 31 out of the 46 patients were RECIST evaluable. The outcomes of those patients were to note that the response rate was 13%, which was four partial responses. But 35% of patients had tumor regression with a disease control rate at 65%. It was clear that there was an enrichment by PRAME positivity for both progression free and overall survival. So those patients who had obvious positivity essentially had a doubling of the PFS and more than the doubling of the OS, 2.1 to 4.1 months for TFS and landmark OS, 40% to 94%. So I think these are quite intriguing data.  It does suggest that for the vast majority of patients, we do see some induction of the antitumor effect, albeit that RECIST might undercall the effect. And so this may become another area where the ctDNA monitoring might be able to help us to understand who is likely to have really long-term benefit from this therapy. And given the number of emerging treatments that we have for melanoma, we might be able to really focus in on that group of patients in terms of optimizing how we would use this drug moving into the future. Dr. Diwakar Davar: So you talked about a response rate, and at first glance, this response rate is a little underwhelming. We're talking about 4 out of 31 RECIST evaluable patients, 13%. So it's in the double digits, but barely. So how enthusiastic are you about the results? How does it contrast with at least the publicly known data from other brain targeting approaches, such as the IMA203 agent, understanding that while they may be all targeting somewhat the same target, they are actually extraordinarily different platforms. One's off the shelf, one's highly customized. How do you contextualize the results? How would it contrast with other cellular approaches?  Dr. Jason Luke: I think it's important, again, to emphasize the point you made, which is that they're very different kinds of treatments. So even though they both target PRAME, they're going to be differently useful, and they could be quite useful for different groups of patients. And so here we see that there is a subfraction of patients who are deriving long-term benefit. And we commonly have an argument in our field about, is overall response rate really a useful monitor that describes a patient-centric outcome? While, of course, patients like to know their tumors are shrinking, what they want the most is for the tumors not to get worse and for them not to pass away from cancer. So I think I'm enthusiastic about these results, but emphasizing the point that we need to better understand who is going to benefit the most from this CD3 bispecific PRAME approach and how we're going to be able to harness that into long term benefit for patients because there's no doubt that an off the shelf therapy has a high degree of value relative to adoptive cell transfer, which sort of requires a big wind up.   So when you say, what does it contrast with? Well, the data for IMA203 has shown more than a 50% response rate in patients with more than 5 lines of therapy for metastatic disease. That really looks quite exciting. And several of those patients are now out for quite an extended period, meaning 2 years or more given only a single dose of IMA203. But again, the caveat being, you have to make the cell product for the patient, and that takes time. You lymphodeplete the patient, not all patients can tolerate that in the refractory disease setting, and then they have to be able to tolerate the reinfusion of the cells. And so this drug, IMC-F106C, looks very promising. Moving into the earlier phase trial that we'll talk about, I think the TCR T cell program has a lot of upsides for patients, especially with refractory disease. And so I think these two different approaches are really on parallel tracks. They both target PRAME, but I don't think they necessarily need to be compared one to one, as if they're going to go head-to-head with each other. Dr. Diwakar Davar: So now we'll talk a little bit about the frontline setting, because on the basis of some of these results, Immunocore is now exploring IMC-F106C frontline melanoma. This trial is actually being presented as a trial in progress at this meeting by Georgina Long and colleagues. Some of us are co-authors in that abstract. And in this study, HLA-A*02:01 positive patients with advanced unresectable melanoma will be randomized one to one to the combination of IMC-F106C, which actually, I think after this meeting will be known as bre-ni in combination with nivolumab versus nivolumab regimens, which will either be nivo or nivo-rela, investigators choice and likely dependent on region. So what do you think of the challenge of this trial? We talked about some of the challenges of the TILVANCE trial earlier. But what is going to be the challenge of this trial and in this setting, particularly given the response rates that we've seen so far? Dr. Jason Luke: Yeah, so, similar to comments we had before, thinking about what the optimal control arm is for a study like this is difficult, and so that'll be important as we think about interpreting the results. One has to assume for the purpose of this conversation that it is a positive trial, and that adding the PRAME bispecific theory does lead to an improvement in progression free survival relative to those in checkpoint alone approaches. And I think the magnitude of that difference is going to be of some relevance. And then I think importantly, also figure out who needs this treatment and who's going to benefit long term are going to be really important considerations.  We alluded to how this drug requires an intensive dosing period at the get go, and so telling patients that they need to come in weekly or bi-weekly initially for some number of weeks before they switch to a longer-term intermittent regimen, that comes with real world considerations for patients, their families, their finances, etc. So the benefit has to be clearly obvious that makes it worthwhile doing that, again, because a default could be giving drugs that we've had for 10 years with the nivolumab and ipilimumab. So there's going to be a lot of cross-trial comparison that is going to necessarily have to take place here to think about what these results really mean in the context of other available therapies.  I think the study is reasonable to do. I think this is a very active agent. There's no doubt there's a subset of patients who seem to benefit a lot from it. And I would just emphasize the point that that's probably going to be the most important thing to really drill down on is under the assumption there's a positive trial, we need to know who those people are so we could optimize giving this kind of a treatment to them. Dr. Diwakar Davar: I guess one important point to underscore what Jason said about potential predictive biomarkers, I think as part of the presentation, Dr. Hamid and colleagues will be talking about a candidate predictive biomarker of this agent, which is potentially class specific and not necessarily agent specific of a T cell signature that potentially could define patients who are more likely to benefit from this agent.  So, Jason, as always, thank you for sharing your expertise and insights with the team today. We certainly look forward to catching up again for our wrap up episode after the annual meeting where we'll talk about some of the data that we could not talk about, particularly the late breaking abstracts and other key advances that will shape the future of, certainly the field of immunotherapy and melanoma, potentially the field of cancer immunotherapy at large. Dr. Jason Luke: Oh, thanks very much for the opportunity. Dr. Diwakar Davar: And thank you to our listeners today. You'll find the links to the abstracts discussed today in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. So thank you, and we'll see you soon.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio      

All about Blackmagic's new cameras–the PYXIS 6K box camera and URSA Cine 12K cinema camera. We cover the new announcements and give our thoughts about the feature set and who these cameras might be for. Also, Blackmagic released a new micro color panel that looks interesting, and Canon seems to be opening up the RF mount….sort of. Want to send us a question or comment, or just learn more about the show? Check out our website at https://cameragearpodcast.com, or email us directly at cameragearpodcast@gmail.com. Some links below to product sites are affiliate links and may result in a commission to the Camera Gear Podcast. Links: Canon is Finally Letting Sigma and Tamron Make RF Mount Lenses [PetaPixel] Blackmagic NAB 2024 Update [YouTube] Podcast: Live from NAB 2024: Blackmagic's CEO on the URSA Cine 12K & Future of AI [No Film School]Also available in podcast apps Davinci Resolve Micro Color Panel Blackmagic URSA Cine 12K Blackmagic PYXIS 6K Blackmagic Video Assist 5” 12G HDR

Found Nates' Channel here: https://www.youtube.com/@NatesFilmTutorials/featured Join me here on Patreon!: https://patreon.com/NigelBarros2nd channel video: https://www.youtube.com/@nigelbarrostoo Follow me on Instagram: https://www.instagram.com/nigelbarros/ Get the BEST film emulation and color correction plugins with 10% off here: https://www.filmconvert.com/purchase/?promoCode=NIGELBARROS Cinematch link: https://www.cinematch.com/purchase/?promoCode=NIGELBARROS --- Support this podcast: https://podcasters.spotify.com/pod/show/longlenspodcast/support

Join Bryan Gee as he sets the stage for the upcoming 30 Years of V tour in Asia, Australia, and New Zealand. With the highly anticipated 30 Years album just around the corner, this episode serves as a tantalising taste of what's to come. Get ready to experience the finest Drum and Bass vibes as we celebrate three decades of V! Stay connected with us on social media and subscribe to the V Podcast on your favorite platform to stay updated on the latest episodes Let the beats roll! 1. Philth, Ella Soop, Christopher Rahman - Tell U No 2. Makoto and L-Side - Settle Down 3. Marky, Makoto and Jasmine Knight - Ma Belle (Lovin You) 4. Sl8r, Slay, JKen, and Pablo - You Be Fine 5. Melinki, Pyxis, T.R.A.C, Collette Warren - Go Back 6. Command Strange and T.R.A.C - By Gones 7. Philth and Luke Truth - Leap of Faith 8. Sl8r, Slay, JKen - Family and Friends 9. Styke, Watch, Steo - Let U Know 10. Motiv - Unusual Suspect 11. Melinki and Motiv - Always 12. Bluemode - Fading 13. Bluemode - Time After Time 14. A-Audio - When I Was Young 15. Zoro - When the Lights Go 16. Carlito - Don't You Know 17. Makoto, L-Side, Solah - Falling 18. Chimpo - Fever 19. RTC and MC Fats - Junglist 20. MC Fats and Inja - Keep Us Apart 21. Paul T and Edward Oberon - Bad Boy 22. Zero T and L-Side - Live and Direct 23. Fox, L-Side and Sl8r - Slammer 24. L-Side and Command Strange - Angry Tune 25. Cloud Lord - Ghost Train 26. Molecular - Cold Hands 27. The Sauce - The Sauce (T>I Remix) 28. Crystal Clear - Temper 29. Serpnt - Fiction 30. Alibi and L-Side - All Rasta 31. Alibi and L-Side - Mad Head 32. Sl8r - The Pillar 33. Sl8r - NFA 34. Level 2 and L-Side - Offline 35. Alibi - Cause and Effect VIP 36. Understand Project 37. Randall - Bionic Man (L-Side Remix) 38. Break - Something Like This 39. Alibi - Majesty 40. L-Side and MC Fats - Love in the Heart 41. Bladerunner - The Chronic 42. Level 2 - Your Body 43. Micky Finn and Vital Elements - Whatever the Weather 44. Paul T, Edward Oberon and Riya - Soul Connected 45. Marky and Solah - Poetry (Makoto Remix)